Integrated Two-Analyte Population Pharmacokinetic Model of Polatuzumab Vedotin in Patients With Non-Hodgkin Lymphoma.

Autor: Lu D; Genentech Inc., South San Francisco, California, USA., Lu T; Genentech Inc., South San Francisco, California, USA., Gibiansky L; QuantPharm LLC, North Potomac, Maryland, USA., Li X; Genentech Inc., South San Francisco, California, USA., Li C; Genentech Inc., South San Francisco, California, USA., Agarwal P; Genentech Inc., South San Francisco, California, USA., Shemesh CS; Genentech Inc., South San Francisco, California, USA., Shi R; Genentech Inc., South San Francisco, California, USA., Dere RC; Genentech Inc., South San Francisco, California, USA., Hirata J; Genentech Inc., South San Francisco, California, USA., Miles D; Genentech Inc., South San Francisco, California, USA., Chanu P; Genentech/Roche, Lyon, France., Girish S; Genentech Inc., South San Francisco, California, USA., Jin JY; Genentech Inc., South San Francisco, California, USA.
Jazyk: angličtina
Zdroj: CPT: pharmacometrics & systems pharmacology [CPT Pharmacometrics Syst Pharmacol] 2020 Jan; Vol. 9 (1), pp. 48-59. Date of Electronic Publication: 2019 Dec 23.
DOI: 10.1002/psp4.12482
Abstrakt: A two-analyte integrated population pharmacokinetic (PK) model that simultaneously describes concentrations of antibody-conjugated monomethyl auristatin E (acMMAE) and unconjugated MMAE following repeated administrations of polatuzumab vedotin (pola) was developed based on data from four clinical studies of pola in patients with non-Hodgkin lymphoma. A two-compartment model with a nonspecific, time-dependent linear clearance, a linear time-dependent exponentially declining clearance, and a Michaelis-Menten clearance provided a good fit of the acMMAE plasma PK profiles. All three acMMAE elimination pathways contributed to the input to the central compartment of unconjugated MMAE, which was also described by a two-compartment model. Population PK parameters, covariate effects, and interindividual variability of model parameters were estimated. The impact of clinically relevant covariates on PK exposures of each analyte were quantified and reported to support key label claims.
(© 2019 The Authors. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje