Pharmacokinetics of mexiletine and its major metabolites, p-hydroxymexiletine and hydroxymethylmexiletine, were studied in 10 healthy subjects after administration of a single oral 400 mg dose. Mexiletine was extensively metabolized to hydroxymethylmexiletine and less to p-hydroxymexiletine. Mean metabolic ratio (Rm) was 0.54 and 0.18 respectively. Peak serum concentrations (Cmax) for mexiletine (0.686 +/- 0.110 micrograms/ml), hydroxymethylmexiletine (0.507 +/- 0.087 micrograms/ml), and p-hydroxymexiletine (0.096 +/- 0.046 micrograms/ml) occurred after 3.0, 4.0 and 4.2 +/- 0.6 h. Disposition parameters for mexiletine were as follows: volume of distribution (V lambda), 5.44 +/- 1.44 l/kg; serum clearance (CL) 8.08 +/- 1.23 ml/min/kg. There were no significant differences in elimination half-life (t1/2) and mean residence time (MRT) for mexiletine and its metabolites. Double-peak phenomenon was observed for all the subjects on elimination phase of mexiletine, hydroxymethylmexiletine and p-hydroxymexiletine.