RENAL, BILIARY AND INTESTINAL CLEARANCE OF SOTALOL ENANTIOMERS IN RATMODEL - EVIDENCE OF INTESTINAL EXSORPTION

Biliary clearance (Cl-b) of sotalol (STL) enantiomers was assessed in anaesthetized Sprague-Dawley rats (419 +/- 9 g, mean +/- SEM, n=4) fol lowing administration of a 10 mgkg(-1) IV dose of the racemate. Cl-b f or S- and R-STL (0.0675 +/- 0.0090 and 0.0662 +/- 0.0089 mLmin(-1) kg( -1), respectively) represented approximately 0.3% of systemic clearanc e (Cl-s) values for S- and R-STL (20.4 +/- 2.2 and 20.7 +/- 2.0 mLmin( -1)kg(-1), respectively). Bile:plasma concentration ratios at 1, 2, an d 3 h post-dose were approximately 1.4, 1.3, and 1 2 for both STL enan tiomers. Renal clearance (Cl-r) and intestinal clearance (Cl-i) of STL enantiomers were assessed in conscious Sprague-Dawley rats (325g, n=4 ) following administration of a 10 mg kg(-1) IV dose of the racemate. STL enantiomers were predominantly eliminated intact in the urine: Cl- r for S- and R-STL (26.3 +/- 3.2 and 28.7 +/- 4.2 mLmin(-1)kg(-1) resp ectively) accounted for approximately 96% of Cl-s, for S- and R-STL (2 7.5 +/- 3.3 and 29.9 +/- 4.2 mLmin(-1)kg(-1), respectively). Approxima tely 4% of the dose was recovered in the faeces, corresponding to Cl-i values of 1.16 +/- 0.17 and 1.26 +/- 0.19 mLmin(-1)kg(-1) for S- and R-STL, respectively. Total recovery of the administered dose in urine and faeces was 99.7 +/- 0.2 and 99.8 +/- 0.5% for S- and R-STL, respec tively. It is concluded from these results in the rat model that (i) S TL enantiomers are predominantly eliminated intact in urine; (ii) STL enantiomers are excreted intact in bile, and to a much larger extent i n the faeces, thus suggesting the presence of intestinal exsorption of STL; (iii) STL does not appear to be metabolized; and (iv) Cl-s, Cl-r , Cl-b, and Cl-i are negligibly stereoselective.