caa a22 4500 475818296 CHVBK 20180406123815.0 cr unu---uuuuu 170329e20000601xx s 000 0 eng 10.1007/s002280000127 doi (NATIONALLICENCE)springer-10.1007/s002280000127 Effect of fluconazole on plasma fluvastatin and pravastatin concentrations [Elektronische Daten] [T. Kantola, J. T. Backman, M. Niemi, K. T. Kivistö, P. J. Neuvonen] 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 I, fluconazole increased the mean area under the plasma fluvastatin concentration-time curve (AUC0-∞) by 84% (P < 0.01), the mean elimination half-life (t 1/2) 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. Springer-Verlag Berlin Heidelberg, 2000 Key words Fluvastatin nationallicence Pravastatin nationallicence Fluconazole nationallicence Kantola T. Department of Clinical Pharmacology, University of Helsinki and Helsinki University Central Hospital, Haartmanink. 4, FIN-00290 Helsinki, Finland e-mail: pertti.neuvonen@huch.fi Tel.: +358-9-47173315; Fax: +358-9-47174039, FI aut Backman J. T. Department of Clinical Pharmacology, University of Helsinki and Helsinki University Central Hospital, Haartmanink. 4, FIN-00290 Helsinki, Finland e-mail: pertti.neuvonen@huch.fi Tel.: +358-9-47173315; Fax: +358-9-47174039, FI aut Niemi M. Department of Clinical Pharmacology, University of Helsinki and Helsinki University Central Hospital, Haartmanink. 4, FIN-00290 Helsinki, Finland e-mail: pertti.neuvonen@huch.fi Tel.: +358-9-47173315; Fax: +358-9-47174039, FI aut Kivistö K. T. Department of Clinical Pharmacology, University of Helsinki and Helsinki University Central Hospital, Haartmanink. 4, FIN-00290 Helsinki, Finland e-mail: pertti.neuvonen@huch.fi Tel.: +358-9-47173315; Fax: +358-9-47174039, FI aut Neuvonen P. J. Department of Clinical Pharmacology, University of Helsinki and Helsinki University Central Hospital, Haartmanink. 4, FIN-00290 Helsinki, Finland e-mail: pertti.neuvonen@huch.fi Tel.: +358-9-47173315; Fax: +358-9-47174039, FI aut https://doi.org/10.1007/s002280000127 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s002280000127 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kantola T. Department of Clinical Pharmacology, University of Helsinki and Helsinki University Central Hospital, Haartmanink. 4, FIN-00290 Helsinki, Finland e-mail: pertti.neuvonen@huch.fi Tel.: +358-9-47173315; Fax: +358-9-47174039, FI aut NATIONALLICENCE 700 1- Backman J. T. Department of Clinical Pharmacology, University of Helsinki and Helsinki University Central Hospital, Haartmanink. 4, FIN-00290 Helsinki, Finland e-mail: pertti.neuvonen@huch.fi Tel.: +358-9-47173315; Fax: +358-9-47174039, FI aut NATIONALLICENCE 700 1- Niemi M. Department of Clinical Pharmacology, University of Helsinki and Helsinki University Central Hospital, Haartmanink. 4, FIN-00290 Helsinki, Finland e-mail: pertti.neuvonen@huch.fi Tel.: +358-9-47173315; Fax: +358-9-47174039, FI aut NATIONALLICENCE 700 1- Kivistö K. T. Department of Clinical Pharmacology, University of Helsinki and Helsinki University Central Hospital, Haartmanink. 4, FIN-00290 Helsinki, Finland e-mail: pertti.neuvonen@huch.fi Tel.: +358-9-47173315; Fax: +358-9-47174039, FI aut NATIONALLICENCE 700 1- Neuvonen P. J. Department of Clinical Pharmacology, University of Helsinki and Helsinki University Central Hospital, Haartmanink. 4, FIN-00290 Helsinki, Finland e-mail: pertti.neuvonen@huch.fi Tel.: +358-9-47173315; Fax: +358-9-47174039, FI aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer