Lack of effect of ketoconazole on the pharmacokinetics of rosuvastatin in healthy subjects
Article first published online: 14 JAN 2003
British Journal of Clinical Pharmacology
Volume 55, Issue 1, pages 94–99, January 2003
How to Cite
Cooper, K. J., Martin, P. D., Dane, A. L., Warwick, M. J., Raza, A. and Schneck, D. W. (2003), Lack of effect of ketoconazole on the pharmacokinetics of rosuvastatin in healthy subjects. British Journal of Clinical Pharmacology, 55: 94–99. doi: 10.1046/j.1365-2125.2003.01720.x
- Issue published online: 14 JAN 2003
- Article first published online: 14 JAN 2003
- Received 25 March,accepted 13 June 2002.
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 Cmax 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.