Lack of pharmacokinetic interactions between pitavastatin and efavirenz or darunavir/ritonavir

Background: The drug-drug interactions between pitavastatin and darunavir/ritonavir (DRV/r) as well as pitavastatin and efavirenz (EFV) were examined in an open-label, parallel-arm, pharmacokinetic (PK) study in HIV-uninfected healthy volunteers. Methods: Subjects received a pitavastatin dose of 2 μg for 4 days, followed by either EFV 600 μg (n = 14) or DRV/r 800/100 μg (n = 14) daily for 10 days, and pitavastatin 2 μg coadministered with EFV 600 μg or DRV/r 800/100 μg for 4 days. Full PK profiles were determined for pitavastatin and its lactone metabolite on days 4 and 18 and for EFV or DRV on days 14 and 18. Results: In the EFV arm, the geometric mean area under the concentration time curve (AUC_0-τ) and C_max of pitavastatin were 85.3 ng h mL^-1 and 15.6 ng/mL, respectively, when given alone, versus 76 ng h mL^-1 and 18.8 ng/mL when coadministered with EFV. The geometric mean ratio for pitavastatin with EFV versus alone was 0.89 [90% confidence interval (CI): 0.73 to 1.09] for AUC_0-τ and 1.20 (90% CI: 0.79 to 1.83) for C_max. In the DRV/r arm, AUC_0-τ and C_max were 62.8 ng h mL^-1 and 24.0 ng/mL, respectively, when pitavastatin was administered alone, versus 56.9 ng h mL^-1 and 23.2 ng/mL when coadministered with DRV/r. The geometric mean ratio for pitavastatin with DRV/r versus alone was 0.91 (90% CI: 0.78 to 1.06) for AUC_0-τ and 0.93 (90% CI: 0.72 to 1.19) for C_max. Conclusions: There were no significant PK interactions between pitavastatin and EFV or DRV/r. No significant safety issues or lipid changes were noted.