Pharmacokinetics of intravenous mexiletine in patients with acute myocardial infarction.

Acute myocardial infarction (AMI) is known to alter the pharmacokinetics of several antiarrhythmic agents. To study the effects of AMI on the kinetics of mexiletine (MEX), a single intravenous dose of 200 mg MEX HCl was infused over 30 min in 11 patients with AMI. The study was performed within 24 h of the onset of pain (study I) and repeated about 2 weeks later in seven patients at discharge (study II). MEX was quantitated in plasma and urine samples by a gas-liquid chromatographic method. The decline of MEX in plasma was three-exponential, with a terminal half-life of 14.7 +/- 3.4 (mean +/- SE) h in study I and 11.3 +/- 2.4 h (p less than 0.05) in study II, in the seven patients studied in both phases. The steady-state volume of distribution averaged 578 +/- 97 L in study I and 415 +/- 33 L in study II (p less than 0.05). The total plasma clearance, renal clearance, and recovery of MEX in urine were similar in the two studies, as was the plasma protein binding of MEX (64 +/- 2 vs. 57 +/- 3%, NS). Thus, an increase in the volume of distribution with consequent prolongation of the elimination half-life of MEX occurs in the acute phase of AMI, whereas the rate of elimination remains unchanged.