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Lack of effect of ketoconazole on the pharmacokinetics of rosuvastatin in healthy subjects
Author(s) -
Cooper Kelvin J.,
Martin Paul D.,
Dane Aaron L.,
Warwick Mike J.,
Raza Ali,
Schneck Dennis W.
Publication year - 2003
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.2003.01720.x
Subject(s) - rosuvastatin , ketoconazole , pharmacokinetics , pharmacology , rosuvastatin calcium , cmax , hydroxymethylglutaryl coa reductase , placebo , hmg coa reductase , crossover study , statin , medicine , reductase , chemistry , enzyme , biochemistry , antifungal , alternative medicine , pathology , dermatology
Aims To examine in vivo the effect of ketoconazole on the pharmacokinetics of rosuvastatin, a 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) reductase inhibitor. Methods This was a randomized, double‐blind, two‐way crossover, placebo‐controlled trial. Healthy male volunteers ( n = 14) received ketoconazole 200 mg or placebo twice daily for 7 days, and rosuvastatin 80 mg was coadministered on day 4 of dosing. Plasma concentrations of rosuvastatin, and active and total HMG‐CoA reductase inhibitors were measured up to 96 h postdose. Results Following coadministration with ketoconazole, rosuvastatin geometric least square mean AUC(0, t ) and C max were unchanged compared with placebo (treatment ratios (90% confidence intervals): 1.016 (0.839, 1.230), 0.954 (0.722, 1.260), respectively). Rosuvastatin accounted for essentially all of the circulating active HMG‐CoA reductase inhibitors and most (> 85%) of the total inhibitors. Ketoconazole did not affect the proportion of circulating active or total inhibitors accounted for by circulating rosuvastatin. Conclusions Ketoconazole did not produce any change in rosuvastatin pharmacokinetics in healthy subjects. The data suggest that neither cytochrome P450 3A4 nor P‐gp‐mediated transport contributes to the elimination of rosuvastatin.