Pharmacokinetics and enterohepatic cycling of atorvastatin in rats

Aim: To determine atorvastatin concentrations in plasma and bile samples of rats and to observe the enterohepatic cycling. Methods: Atorvastatin in plasma was determined by LC-MS in order to assess the degree of absorption after intravenous (iv) or intragastric (ig) administration in the rats. Bile duct was cannulated and bile samples were collected within 12 h after iv or ig administration of atorvastatin, and the cumulative percentage of biliary excretion of atorvastatin in rats was calculated. Rat enterohepatic cycling model was applied to study the process of biliary reabsorption of atorvastatin. The pharmacokinetic parameters were estimated with the computer program 3P87. Results: The concentration-time profiles of atorvastatin after iv or ig administration were best fitted to two-compartment model, and the absolute bioavailability of atorvastatin in rats was found to be 10.2%. Cumulative percentages of biliary excretion within 12 h following iv or ig administration were calculated to be (7.3 ± 1.4) % and (3.3 ± 0.02) %, respectively. In the enterohepatic cycling model, the AUC values of bile-recipient rats and bile-donor rats were estimated to be (26 383.0 ± 9 870.5) ng/mL· min and (2 636.8 ± 1 815. 0) ng/mL· min, respectively. Conclusion: Atorvastatin was poor absorbed follow oral dosing and the findings suggested that enterohepatic cycling of atorvastatin exist in rats after iv administration.