Pharmacokinetics of oral mexiletine in patients with acute myocardial infarction

Summary

To study the effects of acute myocardial infarction on its pharmacokinetics a single oral dose of 400 mg mexiletine HCl was administered to seven patients. The study was performed within 24 h of the onset of pain (Study I) and was repeated 10–14 days later, during the recovery phase (Study II). Mexiletine in plasma and urine was quantified by a GLC method. The peak plasma concentrations of mexiletine were 0.65±0.05 (SEM) µg/ml and 1.08±0.11 µg/ml (p<0.05) in Studies I and II, respectively. The corresponding peak times were 4.68±2.04 h and 1.46±0.17 h (N.S.). The lag time averaged 0.48±0.08 h in Study I and 0.39±0.05 h in Study II (N.S.). The area under the plasma concentration-time curve remained unchanged. The elimination half-life was 15.03±0.61 h and 11.75±0.80 h (p<0.01) in Studies I and II, respectively. The recovery of unchanged mexiletine in urine and its renal clearance was also the same in both studies. The plasma protein binding of mexiletine was similar in Studies I and II (61±2% and 63±3%; N.S.). Thus, the rate of gastrointestinal absorption of mexiletine was definitely slowed in the acute phase of myocardial infarction, whereas the extent of absorption was not altered. The prolongation of the elimination half-life of mexiletine in the acute phase of myocardial infarction is probably related to an increase in its volume of distribution.