Stereoselective Disposition of Mexiletine in Man

Overview

Journal Br J Clin Pharmacol

Specialty Pharmacology

Date 1986 May 1

PMID 3718807

Citations 16

Authors

J Turgeon

M Gilbert

Affiliations

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Abstract

The pharmacokinetics of S-(+)- and R-(-)-mexiletine and of the corresponding conjugates were investigated in six healthy young volunteers after administration of a single 200 mg oral dose of racemic mexiletine hydrochloride. The values for the distribution rate constants as well as for the elimination half-lives of the two enantiomers were similar but the AUC of the S-(+)-enantiomer was always significantly higher (P less than 0.01) than that of the opposite enantiomer. The mean R/S ratios for unchanged mexiletine in serum and in urine were 0.78 +/- 0.12 (s.d.) and 0.80 +/- 0.21, respectively. Urinary excretion of mexiletine conjugates consisted mainly of the R-(-)-enantiomer; the mean R/S enantiomeric ratio over 48 h was 9.65 +/- 3.10. Serum concentrations of the conjugates were measured in three subjects. The mean R/S AUC ratio was 2.94 +/- 0.48 and the renal clearance of the R-(-)-enantiomer was significantly higher (P less than 0.02) than that of the S-(+)-enantiomer.

Citing Articles

Chiral Discrimination of Mexiletine Enantiomers by Capillary Electrophoresis Using Cyclodextrins as Chiral Selectors and Experimental Design Method Optimization.

Carcu-Dobrin M, Hancu G, Papp L, Fulop I Molecules. 2022; 27(17).

PMID: 36080370 PMC: 9458186. DOI: 10.3390/molecules27175603.

Stereoselective binding of mexiletine and ketoprofen enantiomers with human serum albumin domains.

Shi D, Jin Y, Tang Y, Hu H, Xu S, Yu L Acta Pharmacol Sin. 2012; 33(5):710-6.

PMID: 22555373 PMC: 4010353. DOI: 10.1038/aps.2012.8.

Evaluation of the pharmacological activity of the major mexiletine metabolites on skeletal muscle sodium currents.

De Bellis M, De Luca A, Rana F, Cavalluzzi M, Catalano A, Lentini G Br J Pharmacol. 2006; 149(3):300-10.

PMID: 16921388 PMC: 2014276. DOI: 10.1038/sj.bjp.0706867.

Impact of stereoselectivity on the pharmacokinetics and pharmacodynamics of antiarrhythmic drugs.

Mehvar R, Brocks D, Vakily M Clin Pharmacokinet. 2002; 41(8):533-58.

PMID: 12102640 DOI: 10.2165/00003088-200241080-00001.

Clinical pharmacokinetics of mexiletine.

Labbe L, Turgeon J Clin Pharmacokinet. 1999; 37(5):361-84.

PMID: 10589372 DOI: 10.2165/00003088-199937050-00002.

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