Effects of bile salts on the lovastatin pharmacokinetics following oral administration to rats

Abstract

This study aimed to examine the effects of bile salts on pharmacokinetics of lovastatin, which has low bioavailability. Lovastatin solid dispersions were prepared using sodium deoxycholate (NaDC) and sodium glycholate (NaGC) at ratios of 1:19, 1:49, and 1:69. The formulated solid dispersions and control (commercial tablet) were administered to rats and plasma concentrations were determined by a validated LC-MS/MS method. Statistically significant differences were found in Cmax, AUC010, and AUC0∞ values among lovastatin formulations (p<0.05). NaDC-containing formulations revealed higher bioavailabilities than NaGC-containing solid dispersions at ratios of 1:19 and 1:49. Especially, NaDC-containing formulation at a ratio of 1:19 (NaDC19) showed the highest bioavailability. The AUC (both AUC 010 and AUC0∞) of NaDC19 was statistically higher than control and NaDC69 (p<0.05). The AUC values decreased as bile salt concentrations increased. Overall, formulations containing bile salts showed higher AUC values than control, even though all formulations did not show significantly higher AUC. In conclusion, the addition of bile salts to lovastatin could enhance drug bioavailabilities. However, too high concentrations of bile salts could decrease bioavailabilities of lovastatin. © 2011 Informa Healthcare USA, Inc.