Inhibition of human cytochrome P450 isoforms in vitro by zafirlukast.
Article Details
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Shader RI, Granda BW, von Moltke LL, Giancarlo GM, Greenblatt DJ
Inhibition of human cytochrome P450 isoforms in vitro by zafirlukast.
Biopharm Drug Dispos. 1999 Nov;20(8):385-8.
- PubMed ID
- 10870095 [ View in PubMed]
- Abstract
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.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Zafirlukast Cytochrome P450 1A2 Protein Humans UnknownInhibitorDetails Zafirlukast Cytochrome P450 2C19 Protein Humans UnknownInhibitorDetails Zafirlukast Cytochrome P450 2D6 Protein Humans UnknownInhibitorDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareZafirlukastCaffeine The serum concentration of Zafirlukast can be decreased when it is combined with Caffeine. ZafirlukastTheophylline The serum concentration of Zafirlukast can be decreased when it is combined with Theophylline. ZafirlukastDyphylline The serum concentration of Zafirlukast can be decreased when it is combined with Dyphylline. ZafirlukastPentoxifylline The serum concentration of Zafirlukast can be decreased when it is combined with Pentoxifylline. ZafirlukastMercaptopurine The serum concentration of Zafirlukast can be decreased when it is combined with Mercaptopurine.