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

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 microM, while weak inhibition (<30% inhibition) of CYP1A2 and CYP2E1 activities was observed at 100 microM 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.