Biliary secretion of rosuvastatin and bile acids in humans during the absorption phase

Aim: The aim of this study was to investigate the biliary secretion of rosuvastatin in healthy volunteers using an intestinal perfusion method after administration of 10 mg rosuvastatin dispersion in the intestine. Methods: The Loc-I-Gut tube was positioned in the distal duodenum/proximal jejunum and a semi-open segment was created by inflating the proximal balloon in ten volunteers. A dispersion of 10 mg rosuvastatin was administered below the inflated balloon and bile was collected proximally of the inflated balloon. Bile and plasma samples were withdrawn every 20 min during a 4 h period (absorption phase) and additional plasma samples were collected 24 and 48 h post-dose. Results: The study showed that there is a substantial and immediate transport of rosuvastatin into the human bile, with the maximum concentration appearing 42 min after dosing, 39,000 +/- 31,000 ng/ml. Approximately 11% of the administered intestinal dose was recovered in the bile after 240 min. At all time points the biliary concentration exceeded the plasma concentration, and the average bile to plasma ratio was 5200 +/- 9200 (range 89-33,900, median 2000). We were unable to identify any bile-specific metabolites of rosuvastatin in the present study. Conclusion: Rosuvastatin is excreted via the biliary route in humans, and the transport and accumulation of rosuvastatin in bile compared to that in plasma is rapid and extensive. This intestinal perfusion technique offers a successful way to estimate the biliary secretion for drugs, metabolites and endogenous substances during the absorption phase in healthy volunteers. (c) 2006 Elsevier B.V. All rights reserved.