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Title of Journal: Cancer Chemother Pharmacol

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Abbravation: Cancer Chemotherapy and Pharmacology

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Springer-Verlag

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DOI

10.1016/0003-9969(89)90077-0

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1432-0843

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In vitro assessment of cytochrome P450 inhibition

Authors: Jinping Gan Peggy LiuKreyche W Griffith Humphreys
Publish Date: 2011/05/19
Volume: 69, Issue: 1, Pages: 51-56
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Abstract

Tanespimycin did not inhibit the activities of CYP1A2 2A6 2B6 and 2E1 up to a concentration of 60 μM while it moderately inhibited CYP3A4/5 and 2C19 and weakly inhibited CYP2C8 2C9 and 2D6 In addition its inhibition on CYP3A4/5 was timedependent 17AG moderately inhibited the activities of CYP3A4/5 and CYP2C19 but did not inhibit other CYPs up to a concentration of 30 μM The inhibition of CYP3A4/5 by 17AG was not timedependent Tanespimycin and 17AG did not significantly induce the activities of CYP1A2 CYP2B6 or CYP3A4/5 in cultured human hepatocytes at concentrations up to 40 and 20 μM for tanespimycin and 17AG respectivelyTanespimycin together with its active metabolite 17AG are moderate inhibitors of CYP3A4/5 and CYP2C19 but not inducers of CYPs Therefore coadministration of tanespimycin has the potential to increase the exposure of substrates of CYP2C19 and CYP3A4/5

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