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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Inhibition of human cytochrome P450 isoforms in vitro by zafirlukast.

Zafirlukast is a cysteinyl leukotriene antagonist used to treat allergic and exercise-induced asthma. This in vitro study used human liver microsomes to evaluate the inhibitory activity of zafirlukast versus six human cytochrome P450 ( CYP) isoforms. Zafirlukast (0-250 microM) was co-incubated with fixed concentrations of index substrates. Zafirlukast inhibited the hydroxylation of tolbutamide (CYP2C9; mean IC(50)=7.0 microM), triazolam ( CYP3A; IC(50)=20.9 microM) and S-mephenytoin (CYP2C19; IC(50)=32.7 microM), and was a less potent inhibitor of phenacetin O-deethylation (CYP1A2; IC(50)=56 microM) and dextromethorphan O-demethylation (CYP2D6; IC(50)=116 microM). Zafirlukast produced negligible inhibition of CYP2E1. In vitro inhibition of CYP2C9 by zafirlukast is consistent with clinical studies showing impaired clearance of S-warfarin and enhanced anti-thrombotic effects, although the in vitro IC(50) value is higher than the usual range of clinically relevant plasma concentrations. Zafirlukast deserves further clinical study as an inhibitor of other CYP2C9 substrates such as nonsteroidal anti-inflammatory agents, tolbutamide, phenytoin and mestranol. Clinically important inhibition by zafirlukast of other CYP isoforms is not established.[1]


  1. Inhibition of human cytochrome P450 isoforms in vitro by zafirlukast. Shader, R.I., Granda, B.W., von Moltke, L.L., Giancarlo, G.M., Greenblatt, D.J. Biopharmaceutics & drug disposition. (1999) [Pubmed]
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