Lack of effect of ketoconazole on the pharmacokinetics of rosuvastatin in healthy subjects

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 ket...

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Bibliographic Details
Published in:British journal of clinical pharmacology 2003-01, Vol.55 (1), p.94-99
Main Authors: Cooper, Kelvin J., Martin, Paul D., Dane, Aaron L., Warwick, Mike J., Raza, Ali, Schneck, Dennis W.
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antifungal agents
Antifungal Agents - pharmacology
Area Under Curve
Biological and medical sciences
Cross-Over Studies
CYP3A4
Double-Blind Method
Drug Interactions
Fluorobenzenes - pharmacokinetics
General and cellular metabolism. Vitamins
Humans
ketoconazole
Ketoconazole - pharmacology
Male
Medical sciences
Middle Aged
Pharmacology. Drug treatments
Pyrimidines
P‐glycoprotein
rosuvastatin
Rosuvastatin Calcium
Sulfonamides
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Summary: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.
ISSN:0306-5251
1365-2125
DOI:10.1046/j.1365-2125.2003.01720.x