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. 1990 Mar;34(3):402–408. doi: 10.1128/aac.34.3.402

Induction potential of fluconazole toward drug-metabolizing enzymes in rats.

K L Lavrijsen 1, J M Van Houdt 1, D M Van Dyck 1, W E Meuldermans 1, J J Heykants 1
PMCID: PMC171605  PMID: 2334152

Abstract

The induction of drug-metabolizing enzymes in rat liver was studied after subchronic administration of the new triazole antifungal agent fluconazole. The administered doses were 10, 40, and 160 mg/kg per day for 7 days. Fluconazole behaved as a high-magnitude inducer and significantly increased cytochrome P-450 concentrations already at 10 mg/kg (+42%). Cytochrome P-450 induction by fluconazole was dose dependent and reached a value of 302% of the control value at the dose of 160 mg/kg. The induction effects on cytochrome P-450 were also reflected in the drug-metabolizing enzyme activities in hepatic microsomes of pretreated rats. Fluconazole (160 mg/kg per day) preferentially induced the demethylase activities of N,N-dimethylaniline and p-nitroanisole to 258 and 281% of the control values, respectively. The detoxification enzyme UDP-glucuronosyltransferase was significantly lowered by fluconazole at the highest dose. A possible link between the induction potential and the pharmacokinetic properties of triazole antifungal agents is discussed.

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Selected References

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