Drug/drug interaction between lopinavir/ritonavir and rosuvastatin in healthy volunteers

Objectives: 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. Methods: 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. Results: Twenty subjects enrolled, and PK data were available for 15 subjects. Geometric mean (+/- SD) rosuvastatin area under the concentration time curve (AUC)[0,tau] and maximum concentration (C-max) 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 < 0.000 1). The geometric mean ratio was 2.1 (90% confidence interval [Cl]: 1.7 to 2.6) for rosuvastatin AUC[0,tau] and 4.7 (90% Cl: 3.4 to 6.4) for rosuvastatin C-max with lopinavir/ritonavir versus rosuvastatin alone (P < 0.0001). There was I asymptomatic creatine phosphokinase elevation 17 times the upper limit of normal (ULN) and I liver function test elevation between 1.1 and 2.5 times the ULN with the combination. Conclusions: Rosuvastatin low-density lipoprotein reduction was attenuated with lopinavir/ritonavir. Rosuvastatin AUC and C-max 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.