Phenylethylmalonamide (PEMA)

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Abstract
A gas chromatographic method for the determination of primidone and its metabolites, phenylethylmalonamide (PEMA) and phenobarbital in serum, has been described. After a single oral dose of primidone in man, PEMA appeared readily in serum, whereas phenobarbital was undetectable. The biological half-life of primidone after a single dose in man was 3.3 to 7.0 hours with an estimated half-life of 30 hours for PEMA. In epileptic subjects receiving primidone chronically, both PEMA and phenobarbital accumulated in serum. Binding of primidone or PEMA to serum protein was negligible, while phenobarbital was 60% bound. In high doses PEMA showed anticonvulsant activity in rats using the convulsant hexafluorodiethyl ether. In low doses PEMA potentiated the anticonvulsant activity of phenobarbital in rats. In addition, hexobarbital sleeping time in rats was prolonged after injection of PEMA.