Amiodarone pharmacokinetics. II. Disposition kinetics following subchronic administration in rat

✍ Scribed by Scott J. Weir; Clarence T. Ueda

• Publisher: John Wiley and Sons
• Year: 1987
• Tongue: English
• Weight: 577 KB
• Volume: 8
• Category: Article
• ISSN: 0142-2782
• DOI: 10.1002/bdd.2510080505

✦ Synopsis

A 30 mg kg-' intravenous bolus of I4C-amiodarone (19 pCi kg-') was given to male Sprague-Dawley rats pretreated with 0 (vehicle), 25 or 100mgkg-' day-' of amiodarone HCI orally for 37-42 days to determine the effects of dose and duration of administration on the disposition kinetics of amiodarone. Serial blood samples and total urine were collected over 48 hours and assayed for ''C-amiodarone by liquid scintillation counting following separation by HPLC. In all three groups, the blood ''C-amiodarone concentration-time curves declined bioexponentially with terminal half-lives (tfil3) ranging from 14-22 hours. No differences in fi, tlb13, or central compartment volume (V,) were observed between the three groups of rats. In the rats pretreated with 100 mg kg-' day-' of amiodarone HCI for 5-6 weeks, amiodarone clearance (CL) and steady state volume of distribution ( V J were reduceed 52 per cent (12.2 to 5.9mlmin-' kg-') and 41 per cent (11.73 to 6.971 kg-I), respectively. At the lower amiodarone daily dose, no changes in CL or V,, were observed. Negligible levels of radioactivity were detected in the urine. Amiodarone accounted for approximately 3 W O per cent of the total radioactivity in each blood specimen. This study demonstrated that C L and V,, were dose-dependent, and that fi, tl,2p and V , were dose-independent. The results further suggested that the disposition kinetics of amiodarone were independent of the duration of drug administration.