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 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.