title: The effect of amiodarone on theophylline pharmacokinetics in the rat.
abstract: 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.
authors.affiliation: Division of Clinical Pharmacology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania, 19107.
authors.forename: G E
authors.initials: GE
authors.lastname: Larijani
authors.forename: M L
authors.initials: ML
authors.lastname: Rocci
authors.forename: P
authors.initials: P
authors.lastname: Mojaverian
authors.forename: C L
authors.initials: CL
authors.lastname: Saccar
authors.forename: C
authors.initials: C
authors.lastname: Hoholick
authors.forename: P H
authors.initials: PH
authors.lastname: Vlasses