Abstract
BACKGROUND: Rosuvastatin (RSV) is a potent statin with a lower potential for drug interactions. However, recent data have revealed unexpected increases in RSV concentrations with lopinavir/ritonavir. The objective is to study the pharmacokinetic interaction of RSV with atazanavir/ritonavir (ATV/RTV) or fosamprenavir/ritonavir (FPV/RTV). METHODS: In a prospective pharmacokinetic drug interaction study, six HIV-seronegative, healthy adult volunteers received single 10-mg doses of RSV at baseline and after 6 days of ATV/RTV and FPV/RTV, with 6-day washout periods. Plasma concentrations of RSV and its metabolites, N-desmethyl-RSV and RSV-lactone, were measured by using a internally validated tandem mass spectrometric (LC-MS/MS) method over 24 hours. RESULTS: Compared to baseline, the area under the plasma concentration-time curve (AUC0-24h) and maximum plasma concentration (Cmax) of RSV increased by 213% and 600%, respectively, and the time to reach Cmax was shorter (1.75 h vs. 2.91 h) when given with ATV/RTV (P < 0.05). However, coadministration with FPV/RTV did not significantly affect the pharmacokinetics of RSV. The AUC0-24h of N-desmethyl-RSV was not significantly affected by either combinations, but that of RSV-lactone increased (P < 0.05) by 61% and 76% after coadministration with ATV/RTV and FPV/RTV, respectively. CONCLUSION: ATV/RTV significantly increases the plasma concentrations of rosuvastatin, most likely by increasing rosuvastatin's oral bioavailability. Dose limitations of RSV with ATV/RTV may be needed.
Original language | English (US) |
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Pages (from-to) | 605-610 |
Number of pages | 6 |
Journal | Journal of Cardiovascular Pharmacology |
Volume | 51 |
Issue number | 6 |
DOIs | |
State | Published - Jun 2008 |
Keywords
- Atazanavir
- Drug interaction
- Fosamprenavir
- Pharmacokinetics
- Ritonavir
- Rosuvastatin
ASJC Scopus subject areas
- Pharmacology
- Cardiology and Cardiovascular Medicine