Effect of fluconazole on plasma fluvastatin and pravastatin concentrations.
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Kantola T, Backman JT, Niemi M, Kivisto KT, Neuvonen PJ
Effect of fluconazole on plasma fluvastatin and pravastatin concentrations.
Eur J Clin Pharmacol. 2000 Jun;56(3):225-9.
- PubMed ID
- 10952477 [ View in PubMed]
- Abstract
OBJECTIVE: To study the effects of fluconazole on the pharmacokinetics of fluvastatin and pravastatin, two inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. METHODS: Two separate randomised, double-blind, two-phase, crossover studies with identical study design were carried out. In each study, 12 healthy volunteers were given a 4-day pretreatment with oral fluconazole (400 mg on day 1 and 200 mg on days 2-4) or placebo, according to a randomisation schedule. On day 4, a single oral dose of 40 mg fluvastatin (study I) or 40 mg pravastatin (study II) was administered orally. Plasma concentrations of fluvastatin, pravastatin and fluconazole were measured over 24 h. RESULTS: In study 1, fluconazole increased the mean area under the plasma fluvastatin concentration-time curve (AUC0-infinity) by 84% (P < 0.01), the mean elimination half-life (t1/2) of fluvastatin by 80% (P < 0.01) and its mean peak plasma concentration (Cmax) by 44% (P < 0.05). In study II, fluconazole had no significant effect on the pharmacokinetics of pravastatin. CONCLUSIONS: Fluconazole has a significant interaction with fluvastatin. The mechanism of the increased plasma concentrations and prolonged elimination of fluvastatin is probably inhibition of the CYP2C9-mediated metabolism of fluvastatin by fluconazole. Care should be taken if fluconazole or other potent inhibitors of CYP2C9 are prescribed to patients using fluvastatin. However, pravastatin is not susceptible to interactions with fluconazole or other potent CYP2C9 inhibitors.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Fluconazole Cytochrome P450 2C9 Protein Humans UnknownInhibitorDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareFluvastatinFluconazole The metabolism of Fluvastatin can be decreased when combined with Fluconazole. FluvastatinMifepristone The serum concentration of Fluvastatin can be increased when it is combined with Mifepristone.