RENAL, BILIARY AND INTESTINAL CLEARANCE OF SOTALOL ENANTIOMERS IN RAT MODEL: EVIDENCE OF INTESTINAL EXSORPTION

✍ Scribed by Robert A. Carr; Franco M. Pasutto; Robert T. Foster

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 531 KB
• Volume: 17
• Category: Article
• ISSN: 0142-2782
• DOI: 10.1002/(sici)1099-081x(199611)17:8<725::aid-bdd994>3.0.co;2-p

✦ Synopsis

Biliary clearance (C1, ) of sotalol (STL) enantiomers was assessed in anaesthetized Sprague-Dawley rats (419 f 9 g, mean f SEM, n = 4) following administration of a 10mgkg-' IV dose of the racemate. C1b for S-and R-STL (0~0675f0~0090 and 0.0662 +_0.0089 mL min-' kg-I, respectively) represented approximately 0.3% of systemic clearance (Cl,) values for S-and R-STL (20.4k2.2 and 20.7 k 2.0 mL min-' kg-I, respectively). Bi1e:plasma concentration ratios at 1, 2, and 3 h post-dose were approximately 1.4, 1.3, and 1.2 for both STL enantiomers. Renal clearance (Cl,) and intestinal clearance (Cli) of STL enantiomers were assessed in conscious Sprague-Dawley rats (325 g, n = 4) following administration of a lOmg kg-' IV dose of the racemate. STL enantiomers were predominantly eliminated intact in the urine: C1, for S-and R-STL (26.353.2 and 28.7f4.2mLmin-I kg-I, respectively) accounted for approximately 96% of CIS for Sand R-STL (27.5f3.3 and 29.9f4.2mLmin-' kg-I, respectively). Approximately 4% of the dose was recovered in the faeces, corresponding to Cli values of 1.16 f0.17 and 1.26 f0+19mLmin-' kg-I for S-and R-STL, respectively. Total recovery of the administered dose in urine and faeces was 99.7 f 0.2 and 99.8 f 0.5% for S -and R-STL, respectively. It is concluded from these results in the rat model that (i) STL enantiomers are predominantly eliminated intact in urine; (ii) STL enantiomers are excreted intact in bile, and to a much larger extent in the faeces, thus suggesting the presence of intestinal exsorption of STL; (iii) STL does not appear to be metabolized; and (iv) C1, , C1, , Clb, and Cli are negligibly stereoselective.