The pharmacokinetics of fluvastatin, atorvastatin and pravastatin in collagen-induced arthritis rat model

• Main Authors: Ke-Wei Hsu, 許克瑋
• Other Authors: Chun-Jung Lin
• Format: Others
• Language: zh-TW
• Published: 2016
• Online Access: http://ndltd.ncl.edu.tw/handle/95635621648890371884

碩士 === 國立臺灣大學 === 藥學研究所 === 104 === The objective of the present study was to investigate the pharmacokinetic properties of fluvastatin, atorvastatin and pravastatin in collagen-induced arthritis (CIA) rats. When fluvastatin and atorvastatin were given orally, the plasma levels and systemic exposures of fluvastatin and atorvastatin were significantly higher in CIA rats than in control rats. Also, the results from portal vein injection were similar to those of oral doing of fluvastatin and atorvastatin. In contrast, there were no differences in the plasma level and systemic exposure of pravastatin between CIA and control rats. The pharmacokinetic analysis suggested that the increased plasma levels of fluvastatin and atorvastatin may be due to the decreased apparent clearances in CIA rats. Furthermore, the hepatic uptake clearances of fluvastatin and atorvastatin were significantly reduced, while the metabolism of fluvastatin was also slightly inhibited by hepatic microsome in CIA rats. However, the higher plasma levels of fluvastatin and atorvastatin in CIA rats did not cause a significant increase in the levels of AST (aspartate aminotransferase), ALT (alanine aminotransferase), and CK (creatine kinase), compared with control rats. In the part of pravastatin, there were also no differences in hepatotoxicity (as measured for AST and ALT) and myotoxicity (as measured for CK) because of the similar plasma levels in CIA and control rats.