Effects of bile salts on the lovastatin pharmacokinetics following oral administration to rats.
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 C(max), AUC₀₋₁₀, 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 AUC₀₋₁₀ 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.
Kim
Kyunghee
K
College of Pharmacy and Life & Pharmaceutical Sciences, Ewha Womans University, 11-1 Daehyun-Dong, Seodaemun-Gu, Seoul 120-750, Korea.
Yoon
Inkyung
I
Chun
Inkoo
I
Lee
Nayoung
N
Kim
Taekrho
T
Gwak
Hye Sun
HS
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001647:Bile Acids and Salts / Q000737:chemistry / Q000494:pharmacology*; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003840:Deoxycholic Acid / Q000737:chemistry; D004347:Drug Interactions; D008148:Lovastatin / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013607:Tablets / Q000737:chemistry / Q000493:pharmacokinetics
D001647:Bile Acids and Salts; D013607:Tablets; D003840:Deoxycholic Acid; D008148:Lovastatin