title: Lack of interaction between amiodarone and mexiletine in cardiac arrhythmia patients.
abstract: Amiodarone has pharmacokinetic interactions with various therapeutic agents, including phenytoin, flecainide, and cyclosporine. Mexiletine is metabolized by CYP2D6 and CYP1A2. The objective of this study is to evaluate the effect of amiodarone on the pharmacokinetics of mexiletine through its inhibition of various cytochrome P450 (CYP) subtypes. In a series of 181 inpatients with supraventricular tachyarrhythmias, 26 inpatients received mexiletine and amiodarone therapy (MEX + AMD group), and the others received mexiletine therapy (MEX group). In 10 inpatients of the MEX + AMD group, the mexiletine clearance (CL(MEX)/F) before and after coadministration of amiodarone was compared. CL(MEX)/F was also compared in the MEX and MEX + AMD groups after the start of amiodarone therapy. Serum mexiletine, amiodarone, and desethylamiodarone concentrations were measured by an HPLC method. The CL(MEX)/F was estimated by the Bayesian method using population pharmacokinetic analysis. There was no significant difference in CL(MEX)/F before and after 1-month coadministration of amiodarone in 10 inpatients of the MEX + AMD group. Although serum amiodarone and desethylamiodarone concentrations gradually increased with time after the start of amiodarone therapy in these patients, CL(MEX)/F showed no change at 3 and 5 months after the start of amiodarone therapy. There was no significant difference in CL(MEX)/F of the MEX group and the MEX + AMD group. The results suggest that the pharmacokinetics of mexiletine is not affected by amiodarone in patients with cardiac arrhythmias.
authors.affiliation: Department of Pharmacy, National Cardiovascular Center, Suita-city, Osaka, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Yonezawa
authors.forename: Kana
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Ueno
authors.forename: Miho
authors.initials: M
authors.lastname: Tachibana
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hashimoto
authors.forename: Kazuo
authors.initials: K
authors.lastname: Komamura
authors.forename: Shiro
authors.initials: S
authors.lastname: Kamakura
authors.forename: Kunio
authors.initials: K
authors.lastname: Miyatake
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Tanaka
mesh_terms: D000368:Aged; D000638:Amiodarone / Q000097:blood* / Q000627:therapeutic use; D000889:Anti-Arrhythmia Agents / Q000097:blood* / Q000627:therapeutic use; D001145:Arrhythmias, Cardiac / Q000097:blood* / Q000188:drug therapy / Q000201:enzymology; D001499:Bayes Theorem; D001682:Biological Availability; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008801:Mexiletine / Q000097:blood* / Q000627:therapeutic use; D008875:Middle Aged
chemical_list: D000889:Anti-Arrhythmia Agents; D008801:Mexiletine; D003577:Cytochrome P-450 Enzyme System; D000638:Amiodarone