The effect of amiodarone on theophylline pharmacokinetics in the rat

Amiodarone is an investigational antiarrhythmic agent which has been implicated in reducing the activity of the hepatic mixed-function oxidase system. To evaluate this effect further, two groups of six male Sprague-Dawley rats each received theophylline (6 mg/kg, iv) preceded by either normal saline...

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Published in:Pharmaceutical research 1986-06, Vol.3 (3), p.167
Main Authors: Larijani, G E, Rocci, Jr, M L, Mojaverian, P, Saccar, C L, Hoholick, C, Vlasses, P H
Format: Article
Language:English
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Summary:Amiodarone is an investigational antiarrhythmic agent which has been implicated in reducing the activity of the hepatic mixed-function oxidase system. To evaluate this effect further, two groups of six male Sprague-Dawley rats each received theophylline (6 mg/kg, iv) preceded by either normal saline or amiodarone HC1 (100 mg/kg, iv). Blood samples were obtained serially for a period of 6 hr and the sera were assayed for theophylline by high-pressure liquid chromatography (HPLC). In rats pretreated with amiodarone, a significant 45% reduction in the mean (± SD) systemic clearance [0.057 (0.010) vs 0.031 (0.004) liter/hr/kg, P < 0.001] and a greater than 100% increase in the mean elimination half-life [2.03 (0.46) vs 4.29 (0.71) hr, P < 0.001] of theophylline were observed. These data demonstrate an acute inhibitory effect of amiodarone on the hepatic microsomal enzyme system.
ISSN:0724-8741
DOI:10.1023/A:1016366008696