Systolic time intervals in evaluation of the negative inotropic effect after single oral doses of mexiletine and disopyramide.

A placebo-controlled, single blind, crossover study was done to evaluate the inotropic effects of single oral doses of mexiletine and disopyramide assessed by the measurement of Systolic Time Intervals (STI). Each of 8 healthy volunteers received five treatments in random order: 200 and 400 mg mexiletine, 100 and 200 mg disopyramide, and placebo. There was a significant increase in cumulated PEP after 400 mg mexiletine and 200 mg disopyramide. There was no significant change in LVET and QS2. Peak plasma levels were in the lower range of the reputed antiarrythmic levels. Plasma concentration-effect relationships are discussed. Although the study revealed large inter- and intrasubject variability in the measured STIs, it is concluded that a negative inotropic effect was detected despite the low plasma levels of the minor negative inotropic drugs.