PBPK Modeling of the Effect of Reduced Kidney Function on the Pharmacokinetics of Drugs Excreted Renally by Organic Anion Transporters

Autor: Vicky Hsu, Kathleen M. Giacomini, Ping Zhao, Lei Zhang, CH Hsueh, Huang Sm
Rok vydání: 2017
Předmět:
Physiologically based pharmacokinetic modelling
Kidney Disease
Organic anion transporter 1
Renal and urogenital
Renal function
Organic Anion Transporters
Pharmacology
urologic and male genital diseases
Kidney
Kidney Function Tests
030226 pharmacology & pharmacy
Models
Biological
03 medical and health sciences
0302 clinical medicine
Pharmacokinetics
Models
Clinical Research
Predictive Value of Tests
medicine
Humans
Pharmacology (medical)
Computer Simulation
Renal Insufficiency
Pharmacology & Pharmacy
Chronic
Renal Insufficiency
Chronic
biology
Chemistry
Kidney metabolism
Pharmacology and Pharmaceutical Sciences
medicine.disease
Biological
female genital diseases and pregnancy complications
Renal Elimination
medicine.anatomical_structure
Liver
Pharmaceutical Preparations
030220 oncology & carcinogenesis
Sitagliptin
Area Under Curve
biology.protein
Algorithms
Kidney disease
medicine.drug
Zdroj: Clinical pharmacology and therapeutics, vol 103, iss 3
Hsueh, C-H; Hsu, V; Zhao, P; Zhang, L; Giacomini, KM; & Huang, S-M. (2018). PBPK Modeling of the Effect of Reduced Kidney Function on the Pharmacokinetics of Drugs Excreted Renally by Organic Anion Transporters. CLINICAL PHARMACOLOGY & THERAPEUTICS, 103(3), 485-492. doi: 10.1002/cpt.750. UC San Francisco: Retrieved from: http://www.escholarship.org/uc/item/96t7w90t
ISSN: 1532-6535
DOI: 10.1002/cpt.750.
Popis: Altered pharmacokinetics (PK) in subjects with chronic kidney disease (CKD) may lead to dosing adjustment of certain drugs in subjects with CKD. It can be valuable to quantitatively predict PK in CKD for the management of drug dosing in these subjects. We developed physiologically based pharmacokinetic (PBPK) models of seven renally eliminated drugs: adefovir, avibactam, entecavir, famotidine, ganciclovir, oseltamivir carboxylate, and sitagliptin. These drugs are all substrates of renal organic anion transporters (OATs). Drug models verified using PK data from healthy subjects (HS) were coupled with physiological models representing CKD that incorporated prior knowledge of effects of CKD on hepatic and renal elimination. The models reasonably described clinically observed PK changes in subjects with CKD (compared to subjects with normal renal function), with predicted AUC changes within 50% of the observed changes. PBPK models can be used to prospectively predict PK of renally eliminated OAT substrates in subjects with CKD.
Databáze: OpenAIRE
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