Effects of atazanavir/ritonavir or fosamprenavir/ritonavir on the pharmacokinetics of rosuvastatin.
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 (AUC 0-24h) 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 AUC 0-24h 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.


CONCLUSIONS
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.
Busti
Anthony J
AJ
School of Pharmacy, Texas Tech University Health Sciences Center, Dallas, TX 75216, USA. anthony.busti@ttuhsc.edu
Bain
Amy M
AM
Hall
Ronald G
RG
Bedimo
Roger G
RG
Leff
Richard D
RD
Meek
Claudia
C
Mehvar
Reza
R
D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology*; D019540:Area Under Curve; D000069446:Atazanavir Sulfate; D002219:Carbamates / Q000494:pharmacology*; D004338:Drug Combinations; D004347:Drug Interactions; D005260:Female; D005464:Fluorobenzenes / Q000097:blood / Q000493:pharmacokinetics*; D005663:Furans; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D010755:Organophosphates / Q000494:pharmacology*; D011446:Prospective Studies; D011725:Pyridines / Q000494:pharmacology*; D011743:Pyrimidines / Q000097:blood / Q000493:pharmacokinetics*; D019438:Ritonavir / Q000494:pharmacology*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*
D019380:Anti-HIV Agents; D002219:Carbamates; D004338:Drug Combinations; D005464:Fluorobenzenes; D005663:Furans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009842:Oligopeptides; D010755:Organophosphates; D011725:Pyridines; D011743:Pyrimidines; D013449:Sulfonamides; D000069446:Atazanavir Sulfate; D000068718:Rosuvastatin Calcium; D019438:Ritonavir; C426859:fosamprenavir