Survey of Pharmaceutical Industry's Best Practices around In Vitro Transporter Assessment and Implications for Drug Development: Considerations from the International Consortium for Innovation and Quality for Pharmaceutical Development Transporter Working Group.

Autor: Rollison HE; Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom (H.E.R., K.S.F.); Department of Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut (P.M., M.T.); Quantitative Clinical Pharmacology, Development Sciences, UCB Biopharma SRL, Braine-L'Alleud, Belgium (H.C.); NCE Drug Metabolism and Pharmacokinetics, the healthcare business of Merck KGaA, Darmstadt, Germany (Z.F.); Drug Metabolism, Gilead Sciences, Inc. Foster City, California (X.L., Y.L.); Preclinical Sciences and Translational Safety, Janssen R&D LLC, Spring House, Pennsylvania (S.H.P.); Pharmacokinetics, Dynamics and Metabolism, Medicine Design, Worldwide R&D, Pfizer Inc, Groton, Connecticut (C.C.); Pharmacokinetic Sciences, Novartis Institutes for Biomedical Research, East Hanover, New Jersey (I.H.); Clinical Pharmacology Modelling and Simulations, GlaxoSmithKline Research and Development, Collegeville, Pennsylvania (N.T., K.M.M.); IQ Secretariat, Faegre Drinker Biddle & Reath, LLP., Washington DC (J.M.V.); Quantitative, Translational and ADME Sciences, AbbVie Inc., North Chicago, Illinois (D.A.J.B.); Investigative Drug Disposition, Lilly Research Laboratories, Eli Lilly Inc, Indianapolis, Indiana (K.M.H.); Nonclinical Biostatistics, Genentech, Inc., South San Francisco, California (J.B.); ADME and Discovery Toxicity, Merck & Co., Inc., Rahway, New Jersey (X.C.); Departments of Drug Metabolism and Pharmacokinetics (C.E.C.A.H., L.S.) and Clinical Pharmacology (R.S.), Genentech, Inc., South San Francisco, California; Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. South San Francisco, California (C.Y.L.); Department of Drug Metabolism and Pharmacokinetics, Bristol Myers Squibb Research and Development, Princeton, New Jersey (H.S.); DMPK Modeling, IVIVT, Research, GSK, Stevenage, United Kingdom (Ku.T.); Takeda Pharmaceutical Company Limited, Fujisawa, Japan (Ki.T.); and Pharmacokinetics, Dynamics, and Metabolism, Translational Medicine and Early Development, Sanofi US, Bridgewater, NJ (C.X.)., Mitra P; Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom (H.E.R., K.S.F.); Department of Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut (P.M., M.T.); Quantitative Clinical Pharmacology, Development Sciences, UCB Biopharma SRL, Braine-L'Alleud, Belgium (H.C.); NCE Drug Metabolism and Pharmacokinetics, the healthcare business of Merck KGaA, Darmstadt, Germany (Z.F.); Drug Metabolism, Gilead Sciences, Inc. Foster City, California (X.L., Y.L.); Preclinical Sciences and Translational Safety, Janssen R&D LLC, Spring House, Pennsylvania (S.H.P.); Pharmacokinetics, Dynamics and Metabolism, Medicine Design, Worldwide R&D, Pfizer Inc, Groton, Connecticut (C.C.); Pharmacokinetic Sciences, Novartis Institutes for Biomedical Research, East Hanover, New Jersey (I.H.); Clinical Pharmacology Modelling and Simulations, GlaxoSmithKline Research and Development, Collegeville, Pennsylvania (N.T., K.M.M.); IQ Secretariat, Faegre Drinker Biddle & Reath, LLP., Washington DC (J.M.V.); Quantitative, Translational and ADME Sciences, AbbVie Inc., North Chicago, Illinois (D.A.J.B.); Investigative Drug Disposition, Lilly Research Laboratories, Eli Lilly Inc, Indianapolis, Indiana (K.M.H.); Nonclinical Biostatistics, Genentech, Inc., South San Francisco, California (J.B.); ADME and Discovery Toxicity, Merck & Co., Inc., Rahway, New Jersey (X.C.); Departments of Drug Metabolism and Pharmacokinetics (C.E.C.A.H., L.S.) and Clinical Pharmacology (R.S.), Genentech, Inc., South San Francisco, California; Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. South San Francisco, California (C.Y.L.); Department of Drug Metabolism and Pharmacokinetics, Bristol Myers Squibb Research and Development, Princeton, New Jersey (H.S.); DMPK Modeling, IVIVT, Research, GSK, Stevenage, United Kingdom (Ku.T.); Takeda Pharmaceutical Company Limited, Fujisawa, Japan (Ki.T.); and Pharmacokinetics, Dynamics, and Metabolism, Translational Medicine and Early Development, Sanofi US, Bridgewater, NJ (C.X.) pallabi.mitra@boehringer-ingelheim.com., Chanteux H; Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom (H.E.R., K.S.F.); Department of Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut (P.M., M.T.); Quantitative Clinical Pharmacology, Development Sciences, UCB Biopharma SRL, Braine-L'Alleud, Belgium (H.C.); NCE Drug Metabolism and Pharmacokinetics, the healthcare business of Merck KGaA, Darmstadt, Germany (Z.F.); Drug Metabolism, Gilead Sciences, Inc. Foster City, California (X.L., Y.L.); Preclinical Sciences and Translational Safety, Janssen R&D LLC, Spring House, Pennsylvania (S.H.P.); Pharmacokinetics, Dynamics and Metabolism, Medicine Design, Worldwide R&D, Pfizer Inc, Groton, Connecticut (C.C.); Pharmacokinetic Sciences, Novartis Institutes for Biomedical Research, East Hanover, New Jersey (I.H.); Clinical Pharmacology Modelling and Simulations, GlaxoSmithKline Research and Development, Collegeville, Pennsylvania (N.T., K.M.M.); IQ Secretariat, Faegre Drinker Biddle & Reath, LLP., Washington DC (J.M.V.); Quantitative, Translational and ADME Sciences, AbbVie Inc., North Chicago, Illinois (D.A.J.B.); Investigative Drug Disposition, Lilly Research Laboratories, Eli Lilly Inc, Indianapolis, Indiana (K.M.H.); Nonclinical Biostatistics, Genentech, Inc., South San Francisco, California (J.B.); ADME and Discovery Toxicity, Merck & Co., Inc., Rahway, New Jersey (X.C.); Departments of Drug Metabolism and Pharmacokinetics (C.E.C.A.H., L.S.) and Clinical Pharmacology (R.S.), Genentech, Inc., South San Francisco, California; Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. South San Francisco, California (C.Y.L.); Department of Drug Metabolism and Pharmacokinetics, Bristol Myers Squibb Research and Development, Princeton, New Jersey (H.S.); DMPK Modeling, IVIVT, Research, GSK, Stevenage, United Kingdom (Ku.T.); Takeda Pharmaceutical Company Limited, Fujisawa, Japan (Ki.T.); and Pharmacokinetics, Dynamics, and Metabolism, Translational Medicine and Early Development, Sanofi US, Bridgewater, NJ (C.X.)., Fang Z; Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom (H.E.R., K.S.F.); Department of Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut (P.M., M.T.); Quantitative Clinical Pharmacology, Development Sciences, UCB Biopharma SRL, Braine-L'Alleud, Belgium (H.C.); NCE Drug Metabolism and Pharmacokinetics, the healthcare business of Merck KGaA, Darmstadt, Germany (Z.F.); Drug Metabolism, Gilead Sciences, Inc. Foster City, California (X.L., Y.L.); Preclinical Sciences and Translational Safety, Janssen R&D LLC, Spring House, Pennsylvania (S.H.P.); Pharmacokinetics, Dynamics and Metabolism, Medicine Design, Worldwide R&D, Pfizer Inc, Groton, Connecticut (C.C.); Pharmacokinetic Sciences, Novartis Institutes for Biomedical Research, East Hanover, New Jersey (I.H.); Clinical Pharmacology Modelling and Simulations, GlaxoSmithKline Research and Development, Collegeville, Pennsylvania (N.T., K.M.M.); IQ Secretariat, Faegre Drinker Biddle & Reath, LLP., Washington DC (J.M.V.); Quantitative, Translational and ADME Sciences, AbbVie Inc., North Chicago, Illinois (D.A.J.B.); Investigative Drug Disposition, Lilly Research Laboratories, Eli Lilly Inc, Indianapolis, Indiana (K.M.H.); Nonclinical Biostatistics, Genentech, Inc., South San Francisco, California (J.B.); ADME and Discovery Toxicity, Merck & Co., Inc., Rahway, New Jersey (X.C.); Departments of Drug Metabolism and Pharmacokinetics (C.E.C.A.H., L.S.) and Clinical Pharmacology (R.S.), Genentech, Inc., South San Francisco, California; Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. South San Francisco, California (C.Y.L.); Department of Drug Metabolism and Pharmacokinetics, Bristol Myers Squibb Research and Development, Princeton, New Jersey (H.S.); DMPK Modeling, IVIVT, Research, GSK, Stevenage, United Kingdom (Ku.T.); Takeda Pharmaceutical Company Limited, Fujisawa, Japan (Ki.T.); and Pharmacokinetics, Dynamics, and Metabolism, Translational Medicine and Early Development, Sanofi US, Bridgewater, NJ (C.X.)., Liang X; Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom (H.E.R., K.S.F.); Department of Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut (P.M., M.T.); Quantitative Clinical Pharmacology, Development Sciences, UCB Biopharma SRL, Braine-L'Alleud, Belgium (H.C.); NCE Drug Metabolism and Pharmacokinetics, the healthcare business of Merck KGaA, Darmstadt, Germany (Z.F.); Drug Metabolism, Gilead Sciences, Inc. Foster City, California (X.L., Y.L.); Preclinical Sciences and Translational Safety, Janssen R&D LLC, Spring House, Pennsylvania (S.H.P.); Pharmacokinetics, Dynamics and Metabolism, Medicine Design, Worldwide R&D, Pfizer Inc, Groton, Connecticut (C.C.); Pharmacokinetic Sciences, Novartis Institutes for Biomedical Research, East Hanover, New Jersey (I.H.); Clinical Pharmacology Modelling and Simulations, GlaxoSmithKline Research and Development, Collegeville, Pennsylvania (N.T., K.M.M.); IQ Secretariat, Faegre Drinker Biddle & Reath, LLP., Washington DC (J.M.V.); Quantitative, Translational and ADME Sciences, AbbVie Inc., North Chicago, Illinois (D.A.J.B.); Investigative Drug Disposition, Lilly Research Laboratories, Eli Lilly Inc, Indianapolis, Indiana (K.M.H.); Nonclinical Biostatistics, Genentech, Inc., South San Francisco, California (J.B.); ADME and Discovery Toxicity, Merck & Co., Inc., Rahway, New Jersey (X.C.); Departments of Drug Metabolism and Pharmacokinetics (C.E.C.A.H., L.S.) and Clinical Pharmacology (R.S.), Genentech, Inc., South San Francisco, California; Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. South San Francisco, California (C.Y.L.); Department of Drug Metabolism and Pharmacokinetics, Bristol Myers Squibb Research and Development, Princeton, New Jersey (H.S.); DMPK Modeling, IVIVT, Research, GSK, Stevenage, United Kingdom (Ku.T.); Takeda Pharmaceutical Company Limited, Fujisawa, Japan (Ki.T.); and Pharmacokinetics, Dynamics, and Metabolism, Translational Medicine and Early Development, Sanofi US, Bridgewater, NJ (C.X.)., Park SH; Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom (H.E.R., K.S.F.); Department of Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut (P.M., M.T.); Quantitative Clinical Pharmacology, Development Sciences, UCB Biopharma SRL, Braine-L'Alleud, Belgium (H.C.); NCE Drug Metabolism and Pharmacokinetics, the healthcare business of Merck KGaA, Darmstadt, Germany (Z.F.); Drug Metabolism, Gilead Sciences, Inc. Foster City, California (X.L., Y.L.); Preclinical Sciences and Translational Safety, Janssen R&D LLC, Spring House, Pennsylvania (S.H.P.); Pharmacokinetics, Dynamics and Metabolism, Medicine Design, Worldwide R&D, Pfizer Inc, Groton, Connecticut (C.C.); Pharmacokinetic Sciences, Novartis Institutes for Biomedical Research, East Hanover, New Jersey (I.H.); Clinical Pharmacology Modelling and Simulations, GlaxoSmithKline Research and Development, Collegeville, Pennsylvania (N.T., K.M.M.); IQ Secretariat, Faegre Drinker Biddle & Reath, LLP., Washington DC (J.M.V.); Quantitative, Translational and ADME Sciences, AbbVie Inc., North Chicago, Illinois (D.A.J.B.); Investigative Drug Disposition, Lilly Research Laboratories, Eli Lilly Inc, Indianapolis, Indiana (K.M.H.); Nonclinical Biostatistics, Genentech, Inc., South San Francisco, California (J.B.); ADME and Discovery Toxicity, Merck & Co., Inc., Rahway, New Jersey (X.C.); Departments of Drug Metabolism and Pharmacokinetics (C.E.C.A.H., L.S.) and Clinical Pharmacology (R.S.), Genentech, Inc., South San Francisco, California; Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. South San Francisco, California (C.Y.L.); Department of Drug Metabolism and Pharmacokinetics, Bristol Myers Squibb Research and Development, Princeton, New Jersey (H.S.); DMPK Modeling, IVIVT, Research, GSK, Stevenage, United Kingdom (Ku.T.); Takeda Pharmaceutical Company Limited, Fujisawa, Japan (Ki.T.); and Pharmacokinetics, Dynamics, and Metabolism, Translational Medicine and Early Development, Sanofi US, Bridgewater, NJ (C.X.)., Costales C; Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom (H.E.R., K.S.F.); Department of Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut (P.M., M.T.); Quantitative Clinical Pharmacology, Development Sciences, UCB Biopharma SRL, Braine-L'Alleud, Belgium (H.C.); NCE Drug Metabolism and Pharmacokinetics, the healthcare business of Merck KGaA, Darmstadt, Germany (Z.F.); Drug Metabolism, Gilead Sciences, Inc. Foster City, California (X.L., Y.L.); Preclinical Sciences and Translational Safety, Janssen R&D LLC, Spring House, Pennsylvania (S.H.P.); Pharmacokinetics, Dynamics and Metabolism, Medicine Design, Worldwide R&D, Pfizer Inc, Groton, Connecticut (C.C.); Pharmacokinetic Sciences, Novartis Institutes for Biomedical Research, East Hanover, New Jersey (I.H.); Clinical Pharmacology Modelling and Simulations, GlaxoSmithKline Research and Development, Collegeville, Pennsylvania (N.T., K.M.M.); IQ Secretariat, Faegre Drinker Biddle & Reath, LLP., Washington DC (J.M.V.); Quantitative, Translational and ADME Sciences, AbbVie Inc., North Chicago, Illinois (D.A.J.B.); Investigative Drug Disposition, Lilly Research Laboratories, Eli Lilly Inc, Indianapolis, Indiana (K.M.H.); Nonclinical Biostatistics, Genentech, Inc., South San Francisco, California (J.B.); ADME and Discovery Toxicity, Merck & Co., Inc., Rahway, New Jersey (X.C.); Departments of Drug Metabolism and Pharmacokinetics (C.E.C.A.H., L.S.) and Clinical Pharmacology (R.S.), Genentech, Inc., South San Francisco, California; Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. South San Francisco, California (C.Y.L.); Department of Drug Metabolism and Pharmacokinetics, Bristol Myers Squibb Research and Development, Princeton, New Jersey (H.S.); DMPK Modeling, IVIVT, Research, GSK, Stevenage, United Kingdom (Ku.T.); Takeda Pharmaceutical Company Limited, Fujisawa, Japan (Ki.T.); and Pharmacokinetics, Dynamics, and Metabolism, Translational Medicine and Early Development, Sanofi US, Bridgewater, NJ (C.X.)., Hanna I; Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom (H.E.R., K.S.F.); Department of Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut (P.M., M.T.); Quantitative Clinical Pharmacology, Development Sciences, UCB Biopharma SRL, Braine-L'Alleud, Belgium (H.C.); NCE Drug Metabolism and Pharmacokinetics, the healthcare business of Merck KGaA, Darmstadt, Germany (Z.F.); Drug Metabolism, Gilead Sciences, Inc. Foster City, California (X.L., Y.L.); Preclinical Sciences and Translational Safety, Janssen R&D LLC, Spring House, Pennsylvania (S.H.P.); Pharmacokinetics, Dynamics and Metabolism, Medicine Design, Worldwide R&D, Pfizer Inc, Groton, Connecticut (C.C.); Pharmacokinetic Sciences, Novartis Institutes for Biomedical Research, East Hanover, New Jersey (I.H.); Clinical Pharmacology Modelling and Simulations, GlaxoSmithKline Research and Development, Collegeville, Pennsylvania (N.T., K.M.M.); IQ Secretariat, Faegre Drinker Biddle & Reath, LLP., Washington DC (J.M.V.); Quantitative, Translational and ADME Sciences, AbbVie Inc., North Chicago, Illinois (D.A.J.B.); Investigative Drug Disposition, Lilly Research Laboratories, Eli Lilly Inc, Indianapolis, Indiana (K.M.H.); Nonclinical Biostatistics, Genentech, Inc., South San Francisco, California (J.B.); ADME and Discovery Toxicity, Merck & Co., Inc., Rahway, New Jersey (X.C.); Departments of Drug Metabolism and Pharmacokinetics (C.E.C.A.H., L.S.) and Clinical Pharmacology (R.S.), Genentech, Inc., South San Francisco, California; Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. South San Francisco, California (C.Y.L.); Department of Drug Metabolism and Pharmacokinetics, Bristol Myers Squibb Research and Development, Princeton, New Jersey (H.S.); DMPK Modeling, IVIVT, Research, GSK, Stevenage, United Kingdom (Ku.T.); Takeda Pharmaceutical Company Limited, Fujisawa, Japan (Ki.T.); and Pharmacokinetics, Dynamics, and Metabolism, Translational Medicine and Early Development, Sanofi US, Bridgewater, NJ (C.X.)., Thakkar N; Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom (H.E.R., K.S.F.); Department of Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut (P.M., M.T.); Quantitative Clinical Pharmacology, Development Sciences, UCB Biopharma SRL, Braine-L'Alleud, Belgium (H.C.); NCE Drug Metabolism and Pharmacokinetics, the healthcare business of Merck KGaA, Darmstadt, Germany (Z.F.); Drug Metabolism, Gilead Sciences, Inc. Foster City, California (X.L., Y.L.); Preclinical Sciences and Translational Safety, Janssen R&D LLC, Spring House, Pennsylvania (S.H.P.); Pharmacokinetics, Dynamics and Metabolism, Medicine Design, Worldwide R&D, Pfizer Inc, Groton, Connecticut (C.C.); Pharmacokinetic Sciences, Novartis Institutes for Biomedical Research, East Hanover, New Jersey (I.H.); Clinical Pharmacology Modelling and Simulations, GlaxoSmithKline Research and Development, Collegeville, Pennsylvania (N.T., K.M.M.); IQ Secretariat, Faegre Drinker Biddle & Reath, LLP., Washington DC (J.M.V.); Quantitative, Translational and ADME Sciences, AbbVie Inc., North Chicago, Illinois (D.A.J.B.); Investigative Drug Disposition, Lilly Research Laboratories, Eli Lilly Inc, Indianapolis, Indiana (K.M.H.); Nonclinical Biostatistics, Genentech, Inc., South San Francisco, California (J.B.); ADME and Discovery Toxicity, Merck & Co., Inc., Rahway, New Jersey (X.C.); Departments of Drug Metabolism and Pharmacokinetics (C.E.C.A.H., L.S.) and Clinical Pharmacology (R.S.), Genentech, Inc., South San Francisco, California; Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. South San Francisco, California (C.Y.L.); Department of Drug Metabolism and Pharmacokinetics, Bristol Myers Squibb Research and Development, Princeton, New Jersey (H.S.); DMPK Modeling, IVIVT, Research, GSK, Stevenage, United Kingdom (Ku.T.); Takeda Pharmaceutical Company Limited, Fujisawa, Japan (Ki.T.); and Pharmacokinetics, Dynamics, and Metabolism, Translational Medicine and Early Development, Sanofi US, Bridgewater, NJ (C.X.)., Vergis JM; Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom (H.E.R., K.S.F.); Department of Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut (P.M., M.T.); Quantitative Clinical Pharmacology, Development Sciences, UCB Biopharma SRL, Braine-L'Alleud, Belgium (H.C.); NCE Drug Metabolism and Pharmacokinetics, the healthcare business of Merck KGaA, Darmstadt, Germany (Z.F.); Drug Metabolism, Gilead Sciences, Inc. Foster City, California (X.L., Y.L.); Preclinical Sciences and Translational Safety, Janssen R&D LLC, Spring House, Pennsylvania (S.H.P.); Pharmacokinetics, Dynamics and Metabolism, Medicine Design, Worldwide R&D, Pfizer Inc, Groton, Connecticut (C.C.); Pharmacokinetic Sciences, Novartis Institutes for Biomedical Research, East Hanover, New Jersey (I.H.); Clinical Pharmacology Modelling and Simulations, GlaxoSmithKline Research and Development, Collegeville, Pennsylvania (N.T., K.M.M.); IQ Secretariat, Faegre Drinker Biddle & Reath, LLP., Washington DC (J.M.V.); Quantitative, Translational and ADME Sciences, AbbVie Inc., North Chicago, Illinois (D.A.J.B.); Investigative Drug Disposition, Lilly Research Laboratories, Eli Lilly Inc, Indianapolis, Indiana (K.M.H.); Nonclinical Biostatistics, Genentech, Inc., South San Francisco, California (J.B.); ADME and Discovery Toxicity, Merck & Co., Inc., Rahway, New Jersey (X.C.); Departments of Drug Metabolism and Pharmacokinetics (C.E.C.A.H., L.S.) and Clinical Pharmacology (R.S.), Genentech, Inc., South San Francisco, California; Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. South San Francisco, California (C.Y.L.); Department of Drug Metabolism and Pharmacokinetics, Bristol Myers Squibb Research and Development, Princeton, New Jersey (H.S.); DMPK Modeling, IVIVT, Research, GSK, Stevenage, United Kingdom (Ku.T.); Takeda Pharmaceutical Company Limited, Fujisawa, Japan (Ki.T.); and Pharmacokinetics, Dynamics, and Metabolism, Translational Medicine and Early Development, Sanofi US, Bridgewater, NJ (C.X.)., Bow DAJ; Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom (H.E.R., K.S.F.); Department of Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut (P.M., M.T.); Quantitative Clinical Pharmacology, Development Sciences, UCB Biopharma SRL, Braine-L'Alleud, Belgium (H.C.); NCE Drug Metabolism and Pharmacokinetics, the healthcare business of Merck KGaA, Darmstadt, Germany (Z.F.); Drug Metabolism, Gilead Sciences, Inc. Foster City, California (X.L., Y.L.); Preclinical Sciences and Translational Safety, Janssen R&D LLC, Spring House, Pennsylvania (S.H.P.); Pharmacokinetics, Dynamics and Metabolism, Medicine Design, Worldwide R&D, Pfizer Inc, Groton, Connecticut (C.C.); Pharmacokinetic Sciences, Novartis Institutes for Biomedical Research, East Hanover, New Jersey (I.H.); Clinical Pharmacology Modelling and Simulations, GlaxoSmithKline Research and Development, Collegeville, Pennsylvania (N.T., K.M.M.); IQ Secretariat, Faegre Drinker Biddle & Reath, LLP., Washington DC (J.M.V.); Quantitative, Translational and ADME Sciences, AbbVie Inc., North Chicago, Illinois (D.A.J.B.); Investigative Drug Disposition, Lilly Research Laboratories, Eli Lilly Inc, Indianapolis, Indiana (K.M.H.); Nonclinical Biostatistics, Genentech, Inc., South San Francisco, California (J.B.); ADME and Discovery Toxicity, Merck & Co., Inc., Rahway, New Jersey (X.C.); Departments of Drug Metabolism and Pharmacokinetics (C.E.C.A.H., L.S.) and Clinical Pharmacology (R.S.), Genentech, Inc., South San Francisco, California; Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. South San Francisco, California (C.Y.L.); Department of Drug Metabolism and Pharmacokinetics, Bristol Myers Squibb Research and Development, Princeton, New Jersey (H.S.); DMPK Modeling, IVIVT, Research, GSK, Stevenage, United Kingdom (Ku.T.); Takeda Pharmaceutical Company Limited, Fujisawa, Japan (Ki.T.); and Pharmacokinetics, Dynamics, and Metabolism, Translational Medicine and Early Development, Sanofi US, Bridgewater, NJ (C.X.)., Hillgren KM; Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom (H.E.R., K.S.F.); Department of Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut (P.M., M.T.); Quantitative Clinical Pharmacology, Development Sciences, UCB Biopharma SRL, Braine-L'Alleud, Belgium (H.C.); NCE Drug Metabolism and Pharmacokinetics, the healthcare business of Merck KGaA, Darmstadt, Germany (Z.F.); Drug Metabolism, Gilead Sciences, Inc. Foster City, California (X.L., Y.L.); Preclinical Sciences and Translational Safety, Janssen R&D LLC, Spring House, Pennsylvania (S.H.P.); Pharmacokinetics, Dynamics and Metabolism, Medicine Design, Worldwide R&D, Pfizer Inc, Groton, Connecticut (C.C.); Pharmacokinetic Sciences, Novartis Institutes for Biomedical Research, East Hanover, New Jersey (I.H.); Clinical Pharmacology Modelling and Simulations, GlaxoSmithKline Research and Development, Collegeville, Pennsylvania (N.T., K.M.M.); IQ Secretariat, Faegre Drinker Biddle & Reath, LLP., Washington DC (J.M.V.); Quantitative, Translational and ADME Sciences, AbbVie Inc., North Chicago, Illinois (D.A.J.B.); Investigative Drug Disposition, Lilly Research Laboratories, Eli Lilly Inc, Indianapolis, Indiana (K.M.H.); Nonclinical Biostatistics, Genentech, Inc., South San Francisco, California (J.B.); ADME and Discovery Toxicity, Merck & Co., Inc., Rahway, New Jersey (X.C.); Departments of Drug Metabolism and Pharmacokinetics (C.E.C.A.H., L.S.) and Clinical Pharmacology (R.S.), Genentech, Inc., South San Francisco, California; Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. South San Francisco, California (C.Y.L.); Department of Drug Metabolism and Pharmacokinetics, Bristol Myers Squibb Research and Development, Princeton, New Jersey (H.S.); DMPK Modeling, IVIVT, Research, GSK, Stevenage, United Kingdom (Ku.T.); Takeda Pharmaceutical Company Limited, Fujisawa, Japan (Ki.T.); and Pharmacokinetics, Dynamics, and Metabolism, Translational Medicine and Early Development, Sanofi US, Bridgewater, NJ (C.X.)., Brumm J; Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom (H.E.R., K.S.F.); Department of Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut (P.M., M.T.); Quantitative Clinical Pharmacology, Development Sciences, UCB Biopharma SRL, Braine-L'Alleud, Belgium (H.C.); NCE Drug Metabolism and Pharmacokinetics, the healthcare business of Merck KGaA, Darmstadt, Germany (Z.F.); Drug Metabolism, Gilead Sciences, Inc. Foster City, California (X.L., Y.L.); Preclinical Sciences and Translational Safety, Janssen R&D LLC, Spring House, Pennsylvania (S.H.P.); Pharmacokinetics, Dynamics and Metabolism, Medicine Design, Worldwide R&D, Pfizer Inc, Groton, Connecticut (C.C.); Pharmacokinetic Sciences, Novartis Institutes for Biomedical Research, East Hanover, New Jersey (I.H.); Clinical Pharmacology Modelling and Simulations, GlaxoSmithKline Research and Development, Collegeville, Pennsylvania (N.T., K.M.M.); IQ Secretariat, Faegre Drinker Biddle & Reath, LLP., Washington DC (J.M.V.); Quantitative, Translational and ADME Sciences, AbbVie Inc., North Chicago, Illinois (D.A.J.B.); Investigative Drug Disposition, Lilly Research Laboratories, Eli Lilly Inc, Indianapolis, Indiana (K.M.H.); Nonclinical Biostatistics, Genentech, Inc., South San Francisco, California (J.B.); ADME and Discovery Toxicity, Merck & Co., Inc., Rahway, New Jersey (X.C.); Departments of Drug Metabolism and Pharmacokinetics (C.E.C.A.H., L.S.) and Clinical Pharmacology (R.S.), Genentech, Inc., South San Francisco, California; Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. South San Francisco, California (C.Y.L.); Department of Drug Metabolism and Pharmacokinetics, Bristol Myers Squibb Research and Development, Princeton, New Jersey (H.S.); DMPK Modeling, IVIVT, Research, GSK, Stevenage, United Kingdom (Ku.T.); Takeda Pharmaceutical Company Limited, Fujisawa, Japan (Ki.T.); and Pharmacokinetics, Dynamics, and Metabolism, Translational Medicine and Early Development, Sanofi US, Bridgewater, NJ (C.X.)., Chu X; Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom (H.E.R., K.S.F.); Department of Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut (P.M., M.T.); Quantitative Clinical Pharmacology, Development Sciences, UCB Biopharma SRL, Braine-L'Alleud, Belgium (H.C.); NCE Drug Metabolism and Pharmacokinetics, the healthcare business of Merck KGaA, Darmstadt, Germany (Z.F.); Drug Metabolism, Gilead Sciences, Inc. Foster City, California (X.L., Y.L.); Preclinical Sciences and Translational Safety, Janssen R&D LLC, Spring House, Pennsylvania (S.H.P.); Pharmacokinetics, Dynamics and Metabolism, Medicine Design, Worldwide R&D, Pfizer Inc, Groton, Connecticut (C.C.); Pharmacokinetic Sciences, Novartis Institutes for Biomedical Research, East Hanover, New Jersey (I.H.); Clinical Pharmacology Modelling and Simulations, GlaxoSmithKline Research and Development, Collegeville, Pennsylvania (N.T., K.M.M.); IQ Secretariat, Faegre Drinker Biddle & Reath, LLP., Washington DC (J.M.V.); Quantitative, Translational and ADME Sciences, AbbVie Inc., North Chicago, Illinois (D.A.J.B.); Investigative Drug Disposition, Lilly Research Laboratories, Eli Lilly Inc, Indianapolis, Indiana (K.M.H.); Nonclinical Biostatistics, Genentech, Inc., South San Francisco, California (J.B.); ADME and Discovery Toxicity, Merck & Co., Inc., Rahway, New Jersey (X.C.); Departments of Drug Metabolism and Pharmacokinetics (C.E.C.A.H., L.S.) and Clinical Pharmacology (R.S.), Genentech, Inc., South San Francisco, California; Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. South San Francisco, California (C.Y.L.); Department of Drug Metabolism and Pharmacokinetics, Bristol Myers Squibb Research and Development, Princeton, New Jersey (H.S.); DMPK Modeling, IVIVT, Research, GSK, Stevenage, United Kingdom (Ku.T.); Takeda Pharmaceutical Company Limited, Fujisawa, Japan (Ki.T.); and Pharmacokinetics, Dynamics, and Metabolism, Translational Medicine and Early Development, Sanofi US, Bridgewater, NJ (C.X.)., Hop CECA; Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom (H.E.R., K.S.F.); Department of Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut (P.M., M.T.); Quantitative Clinical Pharmacology, Development Sciences, UCB Biopharma SRL, Braine-L'Alleud, Belgium (H.C.); NCE Drug Metabolism and Pharmacokinetics, the healthcare business of Merck KGaA, Darmstadt, Germany (Z.F.); Drug Metabolism, Gilead Sciences, Inc. Foster City, California (X.L., Y.L.); Preclinical Sciences and Translational Safety, Janssen R&D LLC, Spring House, Pennsylvania (S.H.P.); Pharmacokinetics, Dynamics and Metabolism, Medicine Design, Worldwide R&D, Pfizer Inc, Groton, Connecticut (C.C.); Pharmacokinetic Sciences, Novartis Institutes for Biomedical Research, East Hanover, New Jersey (I.H.); Clinical Pharmacology Modelling and Simulations, GlaxoSmithKline Research and Development, Collegeville, Pennsylvania (N.T., K.M.M.); IQ Secretariat, Faegre Drinker Biddle & Reath, LLP., Washington DC (J.M.V.); Quantitative, Translational and ADME Sciences, AbbVie Inc., North Chicago, Illinois (D.A.J.B.); Investigative Drug Disposition, Lilly Research Laboratories, Eli Lilly Inc, Indianapolis, Indiana (K.M.H.); Nonclinical Biostatistics, Genentech, Inc., South San Francisco, California (J.B.); ADME and Discovery Toxicity, Merck & Co., Inc., Rahway, New Jersey (X.C.); Departments of Drug Metabolism and Pharmacokinetics (C.E.C.A.H., L.S.) and Clinical Pharmacology (R.S.), Genentech, Inc., South San Francisco, California; Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. South San Francisco, California (C.Y.L.); Department of Drug Metabolism and Pharmacokinetics, Bristol Myers Squibb Research and Development, Princeton, New Jersey (H.S.); DMPK Modeling, IVIVT, Research, GSK, Stevenage, United Kingdom (Ku.T.); Takeda Pharmaceutical Company Limited, Fujisawa, Japan (Ki.T.); and Pharmacokinetics, Dynamics, and Metabolism, Translational Medicine and Early Development, Sanofi US, Bridgewater, NJ (C.X.)., Lai Y; Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom (H.E.R., K.S.F.); Department of Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut (P.M., M.T.); Quantitative Clinical Pharmacology, Development Sciences, UCB Biopharma SRL, Braine-L'Alleud, Belgium (H.C.); NCE Drug Metabolism and Pharmacokinetics, the healthcare business of Merck KGaA, Darmstadt, Germany (Z.F.); Drug Metabolism, Gilead Sciences, Inc. Foster City, California (X.L., Y.L.); Preclinical Sciences and Translational Safety, Janssen R&D LLC, Spring House, Pennsylvania (S.H.P.); Pharmacokinetics, Dynamics and Metabolism, Medicine Design, Worldwide R&D, Pfizer Inc, Groton, Connecticut (C.C.); Pharmacokinetic Sciences, Novartis Institutes for Biomedical Research, East Hanover, New Jersey (I.H.); Clinical Pharmacology Modelling and Simulations, GlaxoSmithKline Research and Development, Collegeville, Pennsylvania (N.T., K.M.M.); IQ Secretariat, Faegre Drinker Biddle & Reath, LLP., Washington DC (J.M.V.); Quantitative, Translational and ADME Sciences, AbbVie Inc., North Chicago, Illinois (D.A.J.B.); Investigative Drug Disposition, Lilly Research Laboratories, Eli Lilly Inc, Indianapolis, Indiana (K.M.H.); Nonclinical Biostatistics, Genentech, Inc., South San Francisco, California (J.B.); ADME and Discovery Toxicity, Merck & Co., Inc., Rahway, New Jersey (X.C.); Departments of Drug Metabolism and Pharmacokinetics (C.E.C.A.H., L.S.) and Clinical Pharmacology (R.S.), Genentech, Inc., South San Francisco, California; Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. South San Francisco, California (C.Y.L.); Department of Drug Metabolism and Pharmacokinetics, Bristol Myers Squibb Research and Development, Princeton, New Jersey (H.S.); DMPK Modeling, IVIVT, Research, GSK, Stevenage, United Kingdom (Ku.T.); Takeda Pharmaceutical Company Limited, Fujisawa, Japan (Ki.T.); and Pharmacokinetics, Dynamics, and Metabolism, Translational Medicine and Early Development, Sanofi US, Bridgewater, NJ (C.X.)., Li CY; Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom (H.E.R., K.S.F.); Department of Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut (P.M., M.T.); Quantitative Clinical Pharmacology, Development Sciences, UCB Biopharma SRL, Braine-L'Alleud, Belgium (H.C.); NCE Drug Metabolism and Pharmacokinetics, the healthcare business of Merck KGaA, Darmstadt, Germany (Z.F.); Drug Metabolism, Gilead Sciences, Inc. Foster City, California (X.L., Y.L.); Preclinical Sciences and Translational Safety, Janssen R&D LLC, Spring House, Pennsylvania (S.H.P.); Pharmacokinetics, Dynamics and Metabolism, Medicine Design, Worldwide R&D, Pfizer Inc, Groton, Connecticut (C.C.); Pharmacokinetic Sciences, Novartis Institutes for Biomedical Research, East Hanover, New Jersey (I.H.); Clinical Pharmacology Modelling and Simulations, GlaxoSmithKline Research and Development, Collegeville, Pennsylvania (N.T., K.M.M.); IQ Secretariat, Faegre Drinker Biddle & Reath, LLP., Washington DC (J.M.V.); Quantitative, Translational and ADME Sciences, AbbVie Inc., North Chicago, Illinois (D.A.J.B.); Investigative Drug Disposition, Lilly Research Laboratories, Eli Lilly Inc, Indianapolis, Indiana (K.M.H.); Nonclinical Biostatistics, Genentech, Inc., South San Francisco, California (J.B.); ADME and Discovery Toxicity, Merck & Co., Inc., Rahway, New Jersey (X.C.); Departments of Drug Metabolism and Pharmacokinetics (C.E.C.A.H., L.S.) and Clinical Pharmacology (R.S.), Genentech, Inc., South San Francisco, California; Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. South San Francisco, California (C.Y.L.); Department of Drug Metabolism and Pharmacokinetics, Bristol Myers Squibb Research and Development, Princeton, New Jersey (H.S.); DMPK Modeling, IVIVT, Research, GSK, Stevenage, United Kingdom (Ku.T.); Takeda Pharmaceutical Company Limited, Fujisawa, Japan (Ki.T.); and Pharmacokinetics, Dynamics, and Metabolism, Translational Medicine and Early Development, Sanofi US, Bridgewater, NJ (C.X.)., Mahar KM; Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom (H.E.R., K.S.F.); Department of Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut (P.M., M.T.); Quantitative Clinical Pharmacology, Development Sciences, UCB Biopharma SRL, Braine-L'Alleud, Belgium (H.C.); NCE Drug Metabolism and Pharmacokinetics, the healthcare business of Merck KGaA, Darmstadt, Germany (Z.F.); Drug Metabolism, Gilead Sciences, Inc. Foster City, California (X.L., Y.L.); Preclinical Sciences and Translational Safety, Janssen R&D LLC, Spring House, Pennsylvania (S.H.P.); Pharmacokinetics, Dynamics and Metabolism, Medicine Design, Worldwide R&D, Pfizer Inc, Groton, Connecticut (C.C.); Pharmacokinetic Sciences, Novartis Institutes for Biomedical Research, East Hanover, New Jersey (I.H.); Clinical Pharmacology Modelling and Simulations, GlaxoSmithKline Research and Development, Collegeville, Pennsylvania (N.T., K.M.M.); IQ Secretariat, Faegre Drinker Biddle & Reath, LLP., Washington DC (J.M.V.); Quantitative, Translational and ADME Sciences, AbbVie Inc., North Chicago, Illinois (D.A.J.B.); Investigative Drug Disposition, Lilly Research Laboratories, Eli Lilly Inc, Indianapolis, Indiana (K.M.H.); Nonclinical Biostatistics, Genentech, Inc., South San Francisco, California (J.B.); ADME and Discovery Toxicity, Merck & Co., Inc., Rahway, New Jersey (X.C.); Departments of Drug Metabolism and Pharmacokinetics (C.E.C.A.H., L.S.) and Clinical Pharmacology (R.S.), Genentech, Inc., South San Francisco, California; Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. South San Francisco, California (C.Y.L.); Department of Drug Metabolism and Pharmacokinetics, Bristol Myers Squibb Research and Development, Princeton, New Jersey (H.S.); DMPK Modeling, IVIVT, Research, GSK, Stevenage, United Kingdom (Ku.T.); Takeda Pharmaceutical Company Limited, Fujisawa, Japan (Ki.T.); and Pharmacokinetics, Dynamics, and Metabolism, Translational Medicine and Early Development, Sanofi US, Bridgewater, NJ (C.X.)., Salphati L; Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom (H.E.R., K.S.F.); Department of Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut (P.M., M.T.); Quantitative Clinical Pharmacology, Development Sciences, UCB Biopharma SRL, Braine-L'Alleud, Belgium (H.C.); NCE Drug Metabolism and Pharmacokinetics, the healthcare business of Merck KGaA, Darmstadt, Germany (Z.F.); Drug Metabolism, Gilead Sciences, Inc. Foster City, California (X.L., Y.L.); Preclinical Sciences and Translational Safety, Janssen R&D LLC, Spring House, Pennsylvania (S.H.P.); Pharmacokinetics, Dynamics and Metabolism, Medicine Design, Worldwide R&D, Pfizer Inc, Groton, Connecticut (C.C.); Pharmacokinetic Sciences, Novartis Institutes for Biomedical Research, East Hanover, New Jersey (I.H.); Clinical Pharmacology Modelling and Simulations, GlaxoSmithKline Research and Development, Collegeville, Pennsylvania (N.T., K.M.M.); IQ Secretariat, Faegre Drinker Biddle & Reath, LLP., Washington DC (J.M.V.); Quantitative, Translational and ADME Sciences, AbbVie Inc., North Chicago, Illinois (D.A.J.B.); Investigative Drug Disposition, Lilly Research Laboratories, Eli Lilly Inc, Indianapolis, Indiana (K.M.H.); Nonclinical Biostatistics, Genentech, Inc., South San Francisco, California (J.B.); ADME and Discovery Toxicity, Merck & Co., Inc., Rahway, New Jersey (X.C.); Departments of Drug Metabolism and Pharmacokinetics (C.E.C.A.H., L.S.) and Clinical Pharmacology (R.S.), Genentech, Inc., South San Francisco, California; Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. South San Francisco, California (C.Y.L.); Department of Drug Metabolism and Pharmacokinetics, Bristol Myers Squibb Research and Development, Princeton, New Jersey (H.S.); DMPK Modeling, IVIVT, Research, GSK, Stevenage, United Kingdom (Ku.T.); Takeda Pharmaceutical Company Limited, Fujisawa, Japan (Ki.T.); and Pharmacokinetics, Dynamics, and Metabolism, Translational Medicine and Early Development, Sanofi US, Bridgewater, NJ (C.X.)., Sane R; Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom (H.E.R., K.S.F.); Department of Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut (P.M., M.T.); Quantitative Clinical Pharmacology, Development Sciences, UCB Biopharma SRL, Braine-L'Alleud, Belgium (H.C.); NCE Drug Metabolism and Pharmacokinetics, the healthcare business of Merck KGaA, Darmstadt, Germany (Z.F.); Drug Metabolism, Gilead Sciences, Inc. Foster City, California (X.L., Y.L.); Preclinical Sciences and Translational Safety, Janssen R&D LLC, Spring House, Pennsylvania (S.H.P.); Pharmacokinetics, Dynamics and Metabolism, Medicine Design, Worldwide R&D, Pfizer Inc, Groton, Connecticut (C.C.); Pharmacokinetic Sciences, Novartis Institutes for Biomedical Research, East Hanover, New Jersey (I.H.); Clinical Pharmacology Modelling and Simulations, GlaxoSmithKline Research and Development, Collegeville, Pennsylvania (N.T., K.M.M.); IQ Secretariat, Faegre Drinker Biddle & Reath, LLP., Washington DC (J.M.V.); Quantitative, Translational and ADME Sciences, AbbVie Inc., North Chicago, Illinois (D.A.J.B.); Investigative Drug Disposition, Lilly Research Laboratories, Eli Lilly Inc, Indianapolis, Indiana (K.M.H.); Nonclinical Biostatistics, Genentech, Inc., South San Francisco, California (J.B.); ADME and Discovery Toxicity, Merck & Co., Inc., Rahway, New Jersey (X.C.); Departments of Drug Metabolism and Pharmacokinetics (C.E.C.A.H., L.S.) and Clinical Pharmacology (R.S.), Genentech, Inc., South San Francisco, California; Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. South San Francisco, California (C.Y.L.); Department of Drug Metabolism and Pharmacokinetics, Bristol Myers Squibb Research and Development, Princeton, New Jersey (H.S.); DMPK Modeling, IVIVT, Research, GSK, Stevenage, United Kingdom (Ku.T.); Takeda Pharmaceutical Company Limited, Fujisawa, Japan (Ki.T.); and Pharmacokinetics, Dynamics, and Metabolism, Translational Medicine and Early Development, Sanofi US, Bridgewater, NJ (C.X.)., Shen H; Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom (H.E.R., K.S.F.); Department of Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut (P.M., M.T.); Quantitative Clinical Pharmacology, Development Sciences, UCB Biopharma SRL, Braine-L'Alleud, Belgium (H.C.); NCE Drug Metabolism and Pharmacokinetics, the healthcare business of Merck KGaA, Darmstadt, Germany (Z.F.); Drug Metabolism, Gilead Sciences, Inc. Foster City, California (X.L., Y.L.); Preclinical Sciences and Translational Safety, Janssen R&D LLC, Spring House, Pennsylvania (S.H.P.); Pharmacokinetics, Dynamics and Metabolism, Medicine Design, Worldwide R&D, Pfizer Inc, Groton, Connecticut (C.C.); Pharmacokinetic Sciences, Novartis Institutes for Biomedical Research, East Hanover, New Jersey (I.H.); Clinical Pharmacology Modelling and Simulations, GlaxoSmithKline Research and Development, Collegeville, Pennsylvania (N.T., K.M.M.); IQ Secretariat, Faegre Drinker Biddle & Reath, LLP., Washington DC (J.M.V.); Quantitative, Translational and ADME Sciences, AbbVie Inc., North Chicago, Illinois (D.A.J.B.); Investigative Drug Disposition, Lilly Research Laboratories, Eli Lilly Inc, Indianapolis, Indiana (K.M.H.); Nonclinical Biostatistics, Genentech, Inc., South San Francisco, California (J.B.); ADME and Discovery Toxicity, Merck & Co., Inc., Rahway, New Jersey (X.C.); Departments of Drug Metabolism and Pharmacokinetics (C.E.C.A.H., L.S.) and Clinical Pharmacology (R.S.), Genentech, Inc., South San Francisco, California; Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. South San Francisco, California (C.Y.L.); Department of Drug Metabolism and Pharmacokinetics, Bristol Myers Squibb Research and Development, Princeton, New Jersey (H.S.); DMPK Modeling, IVIVT, Research, GSK, Stevenage, United Kingdom (Ku.T.); Takeda Pharmaceutical Company Limited, Fujisawa, Japan (Ki.T.); and Pharmacokinetics, Dynamics, and Metabolism, Translational Medicine and Early Development, Sanofi US, Bridgewater, NJ (C.X.)., Taskar K; Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom (H.E.R., K.S.F.); Department of Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut (P.M., M.T.); Quantitative Clinical Pharmacology, Development Sciences, UCB Biopharma SRL, Braine-L'Alleud, Belgium (H.C.); NCE Drug Metabolism and Pharmacokinetics, the healthcare business of Merck KGaA, Darmstadt, Germany (Z.F.); Drug Metabolism, Gilead Sciences, Inc. Foster City, California (X.L., Y.L.); Preclinical Sciences and Translational Safety, Janssen R&D LLC, Spring House, Pennsylvania (S.H.P.); Pharmacokinetics, Dynamics and Metabolism, Medicine Design, Worldwide R&D, Pfizer Inc, Groton, Connecticut (C.C.); Pharmacokinetic Sciences, Novartis Institutes for Biomedical Research, East Hanover, New Jersey (I.H.); Clinical Pharmacology Modelling and Simulations, GlaxoSmithKline Research and Development, Collegeville, Pennsylvania (N.T., K.M.M.); IQ Secretariat, Faegre Drinker Biddle & Reath, LLP., Washington DC (J.M.V.); Quantitative, Translational and ADME Sciences, AbbVie Inc., North Chicago, Illinois (D.A.J.B.); Investigative Drug Disposition, Lilly Research Laboratories, Eli Lilly Inc, Indianapolis, Indiana (K.M.H.); Nonclinical Biostatistics, Genentech, Inc., South San Francisco, California (J.B.); ADME and Discovery Toxicity, Merck & Co., Inc., Rahway, New Jersey (X.C.); Departments of Drug Metabolism and Pharmacokinetics (C.E.C.A.H., L.S.) and Clinical Pharmacology (R.S.), Genentech, Inc., South San Francisco, California; Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. South San Francisco, California (C.Y.L.); Department of Drug Metabolism and Pharmacokinetics, Bristol Myers Squibb Research and Development, Princeton, New Jersey (H.S.); DMPK Modeling, IVIVT, Research, GSK, Stevenage, United Kingdom (Ku.T.); Takeda Pharmaceutical Company Limited, Fujisawa, Japan (Ki.T.); and Pharmacokinetics, Dynamics, and Metabolism, Translational Medicine and Early Development, Sanofi US, Bridgewater, NJ (C.X.)., Taub M; Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom (H.E.R., K.S.F.); Department of Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut (P.M., M.T.); Quantitative Clinical Pharmacology, Development Sciences, UCB Biopharma SRL, Braine-L'Alleud, Belgium (H.C.); NCE Drug Metabolism and Pharmacokinetics, the healthcare business of Merck KGaA, Darmstadt, Germany (Z.F.); Drug Metabolism, Gilead Sciences, Inc. Foster City, California (X.L., Y.L.); Preclinical Sciences and Translational Safety, Janssen R&D LLC, Spring House, Pennsylvania (S.H.P.); Pharmacokinetics, Dynamics and Metabolism, Medicine Design, Worldwide R&D, Pfizer Inc, Groton, Connecticut (C.C.); Pharmacokinetic Sciences, Novartis Institutes for Biomedical Research, East Hanover, New Jersey (I.H.); Clinical Pharmacology Modelling and Simulations, GlaxoSmithKline Research and Development, Collegeville, Pennsylvania (N.T., K.M.M.); IQ Secretariat, Faegre Drinker Biddle & Reath, LLP., Washington DC (J.M.V.); Quantitative, Translational and ADME Sciences, AbbVie Inc., North Chicago, Illinois (D.A.J.B.); Investigative Drug Disposition, Lilly Research Laboratories, Eli Lilly Inc, Indianapolis, Indiana (K.M.H.); Nonclinical Biostatistics, Genentech, Inc., South San Francisco, California (J.B.); ADME and Discovery Toxicity, Merck & Co., Inc., Rahway, New Jersey (X.C.); Departments of Drug Metabolism and Pharmacokinetics (C.E.C.A.H., L.S.) and Clinical Pharmacology (R.S.), Genentech, Inc., South San Francisco, California; Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. South San Francisco, California (C.Y.L.); Department of Drug Metabolism and Pharmacokinetics, Bristol Myers Squibb Research and Development, Princeton, New Jersey (H.S.); DMPK Modeling, IVIVT, Research, GSK, Stevenage, United Kingdom (Ku.T.); Takeda Pharmaceutical Company Limited, Fujisawa, Japan (Ki.T.); and Pharmacokinetics, Dynamics, and Metabolism, Translational Medicine and Early Development, Sanofi US, Bridgewater, NJ (C.X.)., Tohyama K; Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom (H.E.R., K.S.F.); Department of Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut (P.M., M.T.); Quantitative Clinical Pharmacology, Development Sciences, UCB Biopharma SRL, Braine-L'Alleud, Belgium (H.C.); NCE Drug Metabolism and Pharmacokinetics, the healthcare business of Merck KGaA, Darmstadt, Germany (Z.F.); Drug Metabolism, Gilead Sciences, Inc. Foster City, California (X.L., Y.L.); Preclinical Sciences and Translational Safety, Janssen R&D LLC, Spring House, Pennsylvania (S.H.P.); Pharmacokinetics, Dynamics and Metabolism, Medicine Design, Worldwide R&D, Pfizer Inc, Groton, Connecticut (C.C.); Pharmacokinetic Sciences, Novartis Institutes for Biomedical Research, East Hanover, New Jersey (I.H.); Clinical Pharmacology Modelling and Simulations, GlaxoSmithKline Research and Development, Collegeville, Pennsylvania (N.T., K.M.M.); IQ Secretariat, Faegre Drinker Biddle & Reath, LLP., Washington DC (J.M.V.); Quantitative, Translational and ADME Sciences, AbbVie Inc., North Chicago, Illinois (D.A.J.B.); Investigative Drug Disposition, Lilly Research Laboratories, Eli Lilly Inc, Indianapolis, Indiana (K.M.H.); Nonclinical Biostatistics, Genentech, Inc., South San Francisco, California (J.B.); ADME and Discovery Toxicity, Merck & Co., Inc., Rahway, New Jersey (X.C.); Departments of Drug Metabolism and Pharmacokinetics (C.E.C.A.H., L.S.) and Clinical Pharmacology (R.S.), Genentech, Inc., South San Francisco, California; Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. South San Francisco, California (C.Y.L.); Department of Drug Metabolism and Pharmacokinetics, Bristol Myers Squibb Research and Development, Princeton, New Jersey (H.S.); DMPK Modeling, IVIVT, Research, GSK, Stevenage, United Kingdom (Ku.T.); Takeda Pharmaceutical Company Limited, Fujisawa, Japan (Ki.T.); and Pharmacokinetics, Dynamics, and Metabolism, Translational Medicine and Early Development, Sanofi US, Bridgewater, NJ (C.X.)., Xu C; Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom (H.E.R., K.S.F.); Department of Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut (P.M., M.T.); Quantitative Clinical Pharmacology, Development Sciences, UCB Biopharma SRL, Braine-L'Alleud, Belgium (H.C.); NCE Drug Metabolism and Pharmacokinetics, the healthcare business of Merck KGaA, Darmstadt, Germany (Z.F.); Drug Metabolism, Gilead Sciences, Inc. Foster City, California (X.L., Y.L.); Preclinical Sciences and Translational Safety, Janssen R&D LLC, Spring House, Pennsylvania (S.H.P.); Pharmacokinetics, Dynamics and Metabolism, Medicine Design, Worldwide R&D, Pfizer Inc, Groton, Connecticut (C.C.); Pharmacokinetic Sciences, Novartis Institutes for Biomedical Research, East Hanover, New Jersey (I.H.); Clinical Pharmacology Modelling and Simulations, GlaxoSmithKline Research and Development, Collegeville, Pennsylvania (N.T., K.M.M.); IQ Secretariat, Faegre Drinker Biddle & Reath, LLP., Washington DC (J.M.V.); Quantitative, Translational and ADME Sciences, AbbVie Inc., North Chicago, Illinois (D.A.J.B.); Investigative Drug Disposition, Lilly Research Laboratories, Eli Lilly Inc, Indianapolis, Indiana (K.M.H.); Nonclinical Biostatistics, Genentech, Inc., South San Francisco, California (J.B.); ADME and Discovery Toxicity, Merck & Co., Inc., Rahway, New Jersey (X.C.); Departments of Drug Metabolism and Pharmacokinetics (C.E.C.A.H., L.S.) and Clinical Pharmacology (R.S.), Genentech, Inc., South San Francisco, California; Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. South San Francisco, California (C.Y.L.); Department of Drug Metabolism and Pharmacokinetics, Bristol Myers Squibb Research and Development, Princeton, New Jersey (H.S.); DMPK Modeling, IVIVT, Research, GSK, Stevenage, United Kingdom (Ku.T.); Takeda Pharmaceutical Company Limited, Fujisawa, Japan (Ki.T.); and Pharmacokinetics, Dynamics, and Metabolism, Translational Medicine and Early Development, Sanofi US, Bridgewater, NJ (C.X.)., Fenner KS; Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom (H.E.R., K.S.F.); Department of Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut (P.M., M.T.); Quantitative Clinical Pharmacology, Development Sciences, UCB Biopharma SRL, Braine-L'Alleud, Belgium (H.C.); NCE Drug Metabolism and Pharmacokinetics, the healthcare business of Merck KGaA, Darmstadt, Germany (Z.F.); Drug Metabolism, Gilead Sciences, Inc. Foster City, California (X.L., Y.L.); Preclinical Sciences and Translational Safety, Janssen R&D LLC, Spring House, Pennsylvania (S.H.P.); Pharmacokinetics, Dynamics and Metabolism, Medicine Design, Worldwide R&D, Pfizer Inc, Groton, Connecticut (C.C.); Pharmacokinetic Sciences, Novartis Institutes for Biomedical Research, East Hanover, New Jersey (I.H.); Clinical Pharmacology Modelling and Simulations, GlaxoSmithKline Research and Development, Collegeville, Pennsylvania (N.T., K.M.M.); IQ Secretariat, Faegre Drinker Biddle & Reath, LLP., Washington DC (J.M.V.); Quantitative, Translational and ADME Sciences, AbbVie Inc., North Chicago, Illinois (D.A.J.B.); Investigative Drug Disposition, Lilly Research Laboratories, Eli Lilly Inc, Indianapolis, Indiana (K.M.H.); Nonclinical Biostatistics, Genentech, Inc., South San Francisco, California (J.B.); ADME and Discovery Toxicity, Merck & Co., Inc., Rahway, New Jersey (X.C.); Departments of Drug Metabolism and Pharmacokinetics (C.E.C.A.H., L.S.) and Clinical Pharmacology (R.S.), Genentech, Inc., South San Francisco, California; Department of Pharmacokinetics and Drug Metabolism, Amgen Inc. South San Francisco, California (C.Y.L.); Department of Drug Metabolism and Pharmacokinetics, Bristol Myers Squibb Research and Development, Princeton, New Jersey (H.S.); DMPK Modeling, IVIVT, Research, GSK, Stevenage, United Kingdom (Ku.T.); Takeda Pharmaceutical Company Limited, Fujisawa, Japan (Ki.T.); and Pharmacokinetics, Dynamics, and Metabolism, Translational Medicine and Early Development, Sanofi US, Bridgewater, NJ (C.X.).

Publikováno v: Drug metabolism and disposition: the biological fate of chemicals [Drug Metab Dispos] 2024 Jun 17; Vol. 52 (7), pp. 582-596. Date of Electronic Publication: 2024 Jun 17.

Complete Substrate Inhibition of Cytochrome P450 2C8 by AZD9496, an Oral Selective Estrogen Receptor Degrader.

Autor: Bapiro TE; Oncology (T.E.B., A.S., S.M., M.D., J.W.T.Y., B.J.), Quantitative Clinical Pharmacology, Early Clinical Development (M.H.), and Drug Safety and Metabolism (H.E.R.), IMED Biotech Unit, AstraZeneca, Cambridge, United Kingdom tashinga.bapiro1@astrazeneca.com., Sykes A; Oncology (T.E.B., A.S., S.M., M.D., J.W.T.Y., B.J.), Quantitative Clinical Pharmacology, Early Clinical Development (M.H.), and Drug Safety and Metabolism (H.E.R.), IMED Biotech Unit, AstraZeneca, Cambridge, United Kingdom., Martin S; Oncology (T.E.B., A.S., S.M., M.D., J.W.T.Y., B.J.), Quantitative Clinical Pharmacology, Early Clinical Development (M.H.), and Drug Safety and Metabolism (H.E.R.), IMED Biotech Unit, AstraZeneca, Cambridge, United Kingdom., Davies M; Oncology (T.E.B., A.S., S.M., M.D., J.W.T.Y., B.J.), Quantitative Clinical Pharmacology, Early Clinical Development (M.H.), and Drug Safety and Metabolism (H.E.R.), IMED Biotech Unit, AstraZeneca, Cambridge, United Kingdom., Yates JWT; Oncology (T.E.B., A.S., S.M., M.D., J.W.T.Y., B.J.), Quantitative Clinical Pharmacology, Early Clinical Development (M.H.), and Drug Safety and Metabolism (H.E.R.), IMED Biotech Unit, AstraZeneca, Cambridge, United Kingdom., Hoch M; Oncology (T.E.B., A.S., S.M., M.D., J.W.T.Y., B.J.), Quantitative Clinical Pharmacology, Early Clinical Development (M.H.), and Drug Safety and Metabolism (H.E.R.), IMED Biotech Unit, AstraZeneca, Cambridge, United Kingdom., Rollison HE; Oncology (T.E.B., A.S., S.M., M.D., J.W.T.Y., B.J.), Quantitative Clinical Pharmacology, Early Clinical Development (M.H.), and Drug Safety and Metabolism (H.E.R.), IMED Biotech Unit, AstraZeneca, Cambridge, United Kingdom., Jones B; Oncology (T.E.B., A.S., S.M., M.D., J.W.T.Y., B.J.), Quantitative Clinical Pharmacology, Early Clinical Development (M.H.), and Drug Safety and Metabolism (H.E.R.), IMED Biotech Unit, AstraZeneca, Cambridge, United Kingdom.

Publikováno v: Drug metabolism and disposition: the biological fate of chemicals [Drug Metab Dispos] 2018 Sep; Vol. 46 (9), pp. 1268-1276. Date of Electronic Publication: 2018 Jun 19.