Quantitative Prediction of the Effect of CYP3A Inhibitors and Inducers on Venetoclax Pharmacokinetics Using a Physiologically Based Pharmacokinetic Model.
Autor: | Freise KJ; AbbVie, Inc, North Chicago, IL, USA., Shebley M; AbbVie, Inc, North Chicago, IL, USA., Salem AH; AbbVie, Inc, North Chicago, IL, USA. |
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Jazyk: | angličtina |
Zdroj: | Journal of clinical pharmacology [J Clin Pharmacol] 2017 Jun; Vol. 57 (6), pp. 796-804. Date of Electronic Publication: 2017 Jan 04. |
DOI: | 10.1002/jcph.858 |
Abstrakt: | The objectives of the analysis were to develop and verify a venetoclax physiologically based pharmacokinetic (PBPK) model to predict the effects of cytochrome P450 3A (CYP3A) inhibitors and inducers on the PK of venetoclax and inform dosing recommendations. A minimal PBPK model was developed based on prior in vitro and in vivo clinical data using a "middle-out" approach. The PBPK model was independently verified against clinical studies of the strong CYP3A inhibitor ketoconazole, the strong CYP3A inducer, multiple-dose rifampin, and the steady-state venetoclax PK in chronic lymphocytic leukemia (CLL) subjects by comparing predicted to observed ratios of the venetoclax maximum concentration (C (© 2017, The American College of Clinical Pharmacology.) |
Databáze: | MEDLINE |
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