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.
RCT Entities:
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.
Authors: K Maeda; Y Ikeda; T Fujita; K Yoshida; Y Azuma; Y Haruyama; N Yamane; Y Kumagai; Y Sugiyama Journal: Clin Pharmacol Ther Date: 2011-08-10 Impact factor: 6.875
Authors: Thomas Giessmann; Christiane Modess; Ute Hecker; Michael Zschiesche; Peter Dazert; Christiane Kunert-Keil; Rolf Warzok; Georg Engel; Werner Weitschies; Ingolf Cascorbi; Heyo K Kroemer; Werner Siegmund Journal: Clin Pharmacol Ther Date: 2004-03 Impact factor: 6.875
Authors: I Ieiri; S Suwannakul; K Maeda; H Uchimaru; K Hashimoto; M Kimura; H Fujino; M Hirano; H Kusuhara; S Irie; S Higuchi; Y Sugiyama Journal: Clin Pharmacol Ther Date: 2007-04-25 Impact factor: 6.875