Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2486253 | Journal of Pharmaceutical Sciences | 2010 | 10 Pages |
Abstract
In the treatment of cardiac arrhythmias, amiodarone (AM) has emerged as a primary therapeutic agent. In addition to other cytochrome P450 (CYP), 1A1 and 1A2 facilitate the biotransformation of AM to the pharmacologically and toxicologically active metabolite, desethylamiodarone (DEA). The exposure to polycyclic aromatic hydrocarbons can induce these isoforms. This study was aimed at investigating the effect of CYP1A induction on the disposition of AM, after single and multiple intravenous doses, using β-naphthoflavone (BNF) treated rats to model induction of CYP1A. After a single dose (25âmg/kg), the plasma AUC of DEA were significantly induced (â¼3-fold). With multiple doses, AM AUC0-24âh was significantly reduced in the BNF plasma (30%), lung (35%), liver (48%), kidney (52%), heart (34%), and intestine (43%). In contrast the DEA AUC0-24âh was increased significantly in the BNF plasma (36%), lung (56%), liver (101%), kidney (65%), and heart (73%). The DEA/AM ratios of the AUC0-24âh were increased in the BNF plasma, lung, liver, kidney, and heart by 1.9-, 2.5-, 3.8-, 3.4-, and 2.7-fold, respectively. In both groups of rats, the highest concentrations of AM and DEA were in the lung. Exposure to BNF was shown to increase DEA concentrations in the rat. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:539-548, 2010
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Authors
Marwa E. Elsherbiny, Dion R. (Associate Professor),