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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Kinetics and bioavailability of mexiletine in healthy subjects.

Single-dose kinetics of mexiletine (MEX) was studied in six healthy subjects after three different formulations. The respective doses were 200 mg (intravenous infusion), 400 mg (two conventional capsules), and 432 mg (sustained-release dosage forms). By a three-compartment open model with lag time the kinetic parameters of the drug were calculated from the experimental plasma level data. The mathematical analysis of the processes of distribution and elimination was restricted to the intravenous data only, and the resulting transfer constants were introduced into the evaluations of the oral experiments. With this procedure one common value for the plasma t 1/2 of elimination was obtained (t 1/2 gamma = 6.34 +/- 1.5 hr). Mean values for the total volume of distribution (Vdtot) and the total body clearance (Cltot) were 5.5 l/kg and 10.3 ml/min/kg. After capsules, peak plasma concentrations (Cmax = 0.77 microgram/ml) were reached after 2.2 hr. and the sustained-release form built up a flat maximum of concentration (Cmax = 0.34 microgram/ml) after 9.2 hr. Mexiletine is highly bioavailable, almost identical for the two oral formulations: 87.3% (capsule) and 78.7% (slow release). Under physiologic urinary pH1 7.5% to 9.2% of the dose was excreted unchanged by the kidneys.[1]


  1. Kinetics and bioavailability of mexiletine in healthy subjects. Häselbarth, V., Doevendans, J.E., Wolf, M. Clin. Pharmacol. Ther. (1981) [Pubmed]
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