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  • Title: Potential of pranlukast and zafirlukast in the inhibition of human liver cytochrome P450 enzymes.
    Author: Liu KH, Lee YM, Shon JH, Kim MJ, Lee SS, Yoon YR, Cha IJ, Shin JG.
    Journal: Xenobiotica; 2004 May; 34(5):429-38. PubMed ID: 15370959.
    Abstract:
    1. The potential of zafirlukast to inhibit several human cytochrome P450 enzymes is well known. However, pranlukast, a structural analogue of zafirlukast, has not been studied. Accordingly, the inhibitory potential of pranlukast was evaluated and compared with that of zafirlukast, a known CYP2C9 inhibitor, in in vitro microsomal incubation studies. 2. Both pranlukast and zafirlukast showed moderate inhibition of CYP2C9-catalysed tolbutamide 4-methylhydroxylation, competitively inhibiting tolbutamide 4-methylhydroxylation with estimated mean K(i) values of 3.82 +/- 0.50 and 5.86 +/- 0.08 microM, respectively. 3. Pranlukast had no effect on CYP2C19-catalysed S-mephenytoin 4'-hydroxylation or CYP3A4-catalysed midazolam 1-hydroxylation. However, zafirlukast showed minor inhibition of these reactions. Neither pranlukast nor zafirlukast inhibited CYP1A2-catalysed phenacetin O-deethylation, CYP2D6-catalysed dextromethorphan O-demethylation or CYP2E1-catalysed chlorzoxazone 6-hydroxylation. 4. The results suggest that like zafirlukast, pranlukast also has the potential moderately to inhibit CYP2C9-catalysed tolbutamide 4-methylhydroxylation. Therefore, the inhibitory potential of pranlukast should be considered when it is co-administered with CYP2C9 substrates with narrow therapeutic ranges (e.g. S-warfarin, phenytoin).
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