Plasma Level Studies of Primidone and its Metabolites in the Mouse at Various Stages of Pregnancy

Abstract

1. Mice were treated with a teratogenic dose of primidone (100 mg/kg) by gastric intubation at three different times during pregnancy, viz. days 6-14, days 12-14 on day 14 only. Blood samples were taken on day 14 at 1, 4, 8 and 24 h after dosage. Primidone and its metabolites phenylethylmalondiamide (PEMA), and phenobarbitone, were assayed by g.l.c.

2. There was no accumulation of the parent compound or the metabolites after repeated administration of primidone; each of the substances was cleared from the plasma within 24 h.

3. The rate of metabolism of primidone increased with prolonged treatment. The peak concentration of the metabolites was higher in the two multiple-dose groups than in the single-dose group.

4. The concentration of PEMA exceeded that of primidone between 3-8 h and then began to decrease in the multiple-dose groups, a similar pattern was established for phenobarbitone also, although the concentrations were lower than those of PEMA.