Stereoselective disposition of mexiletine in man.

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Abstract
The pharmacokinetics of S‐(+)‐ and R‐(‐)‐mexiletine and of the corresponding conjugates were investigated in six healthy young volunteers after administration of a single 200 mg oral dose of racemic mexiletine hydrochloride. The values for the distribution rate constants as well as for the elimination half‐lives of the two enantiomers were similar but the AUC of the S‐(+)‐enantiomer was always significantly higher (P less than 0.01) than that of the opposite enantiomer. The mean R/S ratios for unchanged mexiletine in serum and in urine were 0.78 +/‐ 0.12 (s.d.) and 0.80 +/‐ 0.21, respectively. Urinary excretion of mexiletine conjugates consisted mainly of the R‐(‐)‐enantiomer; the mean R/S enantiomeric ratio over 48 h was 9.65 +/‐ 3.10. Serum concentrations of the conjugates were measured in three subjects. The mean R/S AUC ratio was 2.94 +/‐ 0.48 and the renal clearance of the R‐(‐)‐enantiomer was significantly higher (P less than 0.02) than that of the S‐(+)‐enantiomer.