Purpose: As an inhibitor of HMG-CoA reductase that catalyses the first step of cholesterol synthesis, pitavastatin undergoes little hepatic metabolism; however, it is a substrate of uptake and efflux transporters. Since pitavastatin is potentially co-administered with agents that affect transporter activities, the pharmacokinetics of pitavastatin was investigated on the effects of a single-dose rifampin in healthy volunteers.
Methods: Twelve Chinese healthy male volunteers took 4 mg pitavastatin orally with 150 ml water or with a single dose of 600 mg rifampin on separate occasions and the plasma concentrations of pitavastatin were measured over 48 h by HPLC-MS/MS.
Results: A single dose of rifampin significantly increased the mean area under the plasma concentration-time curve(AUC)(0-48 h) and Cmax of pitavastatin by 573.5 %(95%CI, 373.3-773.7 %, p < 0.001) and 819.2 %(95 % CI, 515.4-1123.0 %, p < 0.001) respectively, while significantly decreased the t1/2 and CL/F of pitavastatin by 38.8 % (95 % CI, 18.2-59.4 %, p < 0.001) and 81.4 % (95 % CI, 75.0-87.7 %, p < 0.001) respectively.
Conclusions: Co-administration of pitavastatin with a single dose of rifampin resulted in a significant increase in plasma levels of pitavastatin in Chinese healthy subjects.