Mexiletine kinetics in healthy subjects taking cimetidine

Cimetidine, a commonly used H 2 ‐receptor antagonist, was found to interact adversely with many drugs, including class I antiarrhythmics such as lidocaine and quinidine. To test the effect of cimetidine on the kinetics of mexiletine, a class I antiarrhythmic similar to lidocaine, the absorption and disposition of mexiletine were followed in six healthy subjects before and after 1 week of cimetidine, 300 mg by mouth four times a day. Cimetidine did not alter the distribution and elimination of mexiletine, as shown by similar mean kinetics including total body clearance, AUC, and the elimination t½before and after cimetidine treatment. Cimetidine did have a significant effect on mexiletine absorption, as demonstrated by a longer mean absorption t½ (from 0.20 ± 0.14 to 0.61 ± 0.35 hours), a longer mean time to peak mexiletine concentration (from 1.13 ± 0.31 to 1.88 ± 0.83 hours), and decreased mexiletine plasma concentration (from 0.74 ± 0.19 to 0.59 ± 0.15 mg/ml). We conclude that cimetidine does not alter the disposition of oral mexiletine in normal subjects. Clinical Pharmacology and Therapeutics (1985) 37 , 669–673; doi: 10.1038/clpt.1985.109