Effects of Steady-State Lopinavir/Ritonavir on the Pharmacokinetics of Pitavastatin in Healthy Adult Volunteers

Objectives: Pitavastatin, a statin recently approved in the United States, has a potential benefit of reduced risk of cytochrome P450 (CYP)-mediated drug-drug interaction due to minimal metabolism by the CYP system. The primary objective was to investigate pharmacokinetic (PK) effects of lopinavir/ritonavir 400 mg/100 mg twice daily on pitavastatin 4 mg when coadministered. Design: This was an open-label one-arm study. Method: Pitavastatin 4 mg was administered once daily (days 1-5 and days 20-24). Lopinavir/ritonavir 400 mg/100 mg was administered twice daily (days 9-24). Plasma samples for PK assessments were collected on days 5, 19, and 24. Plasma concentrations of analytes were determined by liquid chromatography with tandem mass spectrometric detection methods. Results: PK data were available for 23 of 24 subjects enrolled. For pitavastatin, area under the concentration time curve (AUC(0-tau)) and maximum concentration (C-max) were 136.8 +/- 52.9 ng/h(-1)/mL(-1) and 58.6 +/- 30.4 ng/mL, respectively, when given alone, versus 113.9 +/- 53.8 ng/h(-1)/mL(-1) and 58.2 +/- 32.7 ng/mL when combined with lopinavir/ritonavir. The geometric mean ratio for AUC(0-tau) for pitavastatin with lopinavir/ritonavir versus pitavastatin alone was 80.0 (90% confidence interval: 73.4 to 87.3) and C-max was 96.1 (90% confidence interval: 83.6 to 110.4). Median T-max of pitavastatin was approximately 0.5 hours for both treatments. The PK effect of pitavastatin on lopinavir/ritonavir was minimal. No significant safety issues were reported. Conclusions: The effect on exposures when pitavastatin and lopinavir/ritonavir are coadministered was minimal. Concomitant use of pitavastatin and lopinavir/ritonavir was safe and well tolerated in healthy adult volunteers.