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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 5/2010

Open Access 01-04-2010 | Short Communication

In vitro assessment of cytochrome P450 inhibition and induction potential of azacitidine

Published in: Cancer Chemotherapy and Pharmacology | Issue 5/2010

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Abstract

Purpose

To assess the potential inhibitory and inductive effects of azacitidine on cytochrome P450 isozymes in vitro.

Methods

The inhibitory effects of azacitidine on various CYP isozymes were determined in human liver microsomes. In addition, the ability of azacitidine to induce CYP enzymes in cultured human hepatocytes was evaluated.

Results

Azacitidine did not inhibit CYP2B6-, CYP2C8-, CYP2C9-, CYP2C19-, CYP2D6-, and CYP3A4-mediated activities in human liver microsomes up to a concentration of 100 μM, while weak inhibition (<30% inhibition) of CYP1A2 and CYP2E1 activities was observed at 100 μM azacitidine. In vitro azacitidine did not induce CYP1A2, CYP2C19, or CYP3A4/5 activities in cultured human hepatocytes.

Conclusions

Azacitidine is not an inhibitor or inducer of the cytochrome P450 isozymes tested; therefore, clinically relevant pharmacokinetic drug–drug interactions are unlikely to occur between azacitidine and co-administered substrates of these CYP isozymes.
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Metadata
Title
In vitro assessment of cytochrome P450 inhibition and induction potential of azacitidine
Publication date
01-04-2010
Published in
Cancer Chemotherapy and Pharmacology / Issue 5/2010
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-010-1245-9

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