Pharmacokinetics of phenylethylmalonamide (PEMA) after oral and intravenous administration.

Abstract

The pharmacokinetics of phenylethylmalonamide (PEMA), one of the major metabolites of the antiepileptic drug primidone, have been studied in 6 healthy volunteers after administration of single 500mg intravenous and oral doses. Following intravenous administration, after a very short distributive phase (t1/2 = 0.23-0.53h), the decline of the log-PEMA concentration with respect to time appeared linear. The pharmacokinetic parameters, calculated according to a 1-compartment open model, showed the following values (mean +/- SD): terminal half-life, 15.7 +/- 3.4h; apparent volume of distribution, 0.69 +/- 0.10 L/kg; total serum clearance, 31.3 +/- 6.6 ml/h/kg. After oral administration, peak serum concentrations occurred at 0.5 to 4 hours and the oral bioavailability was 86.4 to 95.9%.