TY - JOUR T1 - Biliary Excretion and Enterohepatic Cycling of R- and S-Flurbiprofen in the Rat JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 428 LP - 430 VL - 25 IS - 4 AU - Stéphane L. Eeckhoudt AU - Pierre A. Evrard AU - Roger K. Verbeeck Y1 - 1997/04/01 UR - http://dmd.aspetjournals.org/content/25/4/428.abstract N2 - According to a previously published report, R- and S-flurbiprofen glucuronides were excreted in the bile after iv administration of the pure enantiomers, but only R-flurbiprofen seemed to undergo enterohepatic cycling. To study the possible stereospecificity in the enterohepatic cycling of flurbiprofen (FL), we investigated the pharmacokinetics of R- and S-FL in control and bile-duct cannulated rats after iv administration of racemic FL (20 mg·kg−1). FL pharmacokinetics were highly stereospecific in control rats: plasma clearance (CL) was much higher and distribution volume (Vd) larger for R-FL (2.60 ± 0.51 ml·min−1·kg−1 and 500 ± 59 ml·kg−1, respectively) as compared with S-FL (CL: 0.72 ± 0.10 ml·min−1·kg−1, Vd: 312 ± 12 ml·kg−1). Renal excretion of the R- and S-FL glucuronides was extremely small (<0.5%), whereas biliary excretion accounted for 8.3 ± 1.8% (R-FL glucuronide) and 14.3 ± 2.4% (S-FL glucuronide) of the administered dose. Bile-duct cannulation significantly increased CL of S-FL (0.90 ± 0.10 ml·min−1·kg−1 compared with 0.72 ± 0.10 ml·min−1·kg−1 in control rats,p <0.05), whereas CL of R-FL was not affected. Paired rat experiments in which the bile of the first rat was deviated into the duodenum of the second rat demonstrated measurable plasma concentrations of R- and S-FL in the receiver rat after iv administration of 20 mg·kg−1 R, S-FL to the donor rat. Our results clearly show that R- and S-FL glucuronides are excreted via the bile and subsequently undergo hydrolysis followed by reabsorption of both R- and S-FL. The American Society for Pharmacology and Experimental Therapeutics ER -