Effects of atazanavir/ritonavir or fosamprenavir/ritonavir on the pharmacokinetics of rosuvastatin

Anthony J. Busti, Amy M. Bain, Ronald G. Hall, Roger G. Bedimo, Richard D. Leff, Claudia Meek, Reza Mehvar

Research output: Contribution to journalArticle

77 Scopus citations

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 languageEnglish (US)
Pages (from-to)605-610
Number of pages6
JournalJournal of Cardiovascular Pharmacology
Volume51
Issue number6
DOIs
Publication statusPublished - Jun 2008

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Keywords

  • Atazanavir
  • Drug interaction
  • Fosamprenavir
  • Pharmacokinetics
  • Ritonavir
  • Rosuvastatin

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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