This open-label, single-arm, pharmacokinetic (PK) study in HIV-seronegative volunteers evaluated the bioequivalence of rosuvastatin and lopinavir/ritonavir when administered alone and in combination. Tolerability and lipid changes were also assessed.
Subjects took 20 mg of rosuvastatin alone for 7 days, then lopinavir/ritonavir alone for 10 days, and then the combination for 7 days. Intensive PK sampling was performed on days 7, 17, and 24.
Twenty subjects enrolled, and PK data were available for 15 subjects. Geometric mean (±SD) rosuvastatin area under the concentration time curve (AUC)[0,τ] and maximum concentration (Cmax) were 47.6 ng·h/mL (±15.3) and 4.34 ng/mL (±1.8), respectively, when given alone versus 98.8 ng·h/mL (±65.5) and 20.2 ng/mL (±16.9) when combined with lopinavir/ritonavir (P < 0.0001). The geometric mean ratio was 2.1 (90% confidence interval [CI]: 1.7 to 2.6) for rosuvastatin AUC[0,τ] and 4.7 (90% CI: 3.4 to 6.4) for rosuvastatin Cmax with lopinavir/ritonavir versus rosuvastatin alone (P < 0.0001). There was 1 asymptomatic creatine phosphokinase elevation 17 times the upper limit of normal (ULN) and 1 liver function test elevation between 1.1 and 2.5 times the ULN with the combination.
Rosuvastatin low-density lipoprotein reduction was attenuated with lopinavir/ritonavir. Rosuvastatin AUC and Cmax were unexpectedly increased 2.1- and 4.7-fold in combination with lopinavir/ritonavir. Rosuvastatin and lopinavir/ritonavir should be used with caution until the safety, efficacy, and appropriate dosing of this combination have been demonstrated in larger populations.
From the *Department of Pharmaceutical Sciences, University of Colorado Denver, Denver, CO; †Divisions of Pharmacology and Toxicology and Infectious Diseases, University of Colorado Denver, Denver, CO; ‡Department of Preventive Medicine and Biometrics, University of Colorado Denver, Denver, CO; and the §Department of Pharmacy, University of Colorado Hospital, Denver, CO.
Received for publication June 29, 2007; accepted October 30, 2007.
Research supported by a grant from the Investigators-Sponsored Study Program of Astra Zeneca and grant M01 RR00051 from the NIH General Clinical Research Center.
Data were presented as a poster at the 14th Conference on Retroviruses and Opportunistic Infections, February 25-28, 2007, Los Angeles, CA (abstract 564).
Correspondence to: Dorie W. Hoody, PharmD, University of Colorado Hospital, Health Sciences Library, 12950 E. Montview Blvd., CB A003, PO Box 6508, Aurora, CO 80045 (e-mail: email@example.com).