Kinetics of primidone metabolism and excretion in children.

The metabolism and excretion of orally administered primidone was studied in 12 children, aged 7 to 14 yr during long-term dosing. Plasma concentrations of primidone (Pr) peaked at 4 to 6 hr and declined exponentially from 6 to 24 hr, with half-life (t1/2) values ranging from 4.5 to 11 hr. A mean of 92% (72% to 123%) of the administered dose was recovered within 24 hr from the urine as Pr and its metabolites. Of the total Pr daily dose, 42.3% (15.2% to 65.9%) was recovered as unchanged drug, 45.2% (16.3% to 65.3%) as phenylethylmalonamide (PEMA), and 4.9% (1.1% to 8.0%) as phenobarbital (Pb). The mean rate constant for conversion of Pr to PEMA (K1) was 0.0424 hr-1, for conversion of Pr to Pb (K2) was 0.0045 hr-1, and for excretion of unchanged Pr (K3) was 0.0389 hr-1. Of Pb excreted, 43% (13% to 100%) was unchanged, 15% (0% to 27%) was unconjugated p-OH Pb, 20% (0% to 44%) was conjugated p-OH Pb, and 22% (0% to 33%) was conjugated 3,4-OH Pb. KE appears to be important determinant of the steady-state plasma concentration of Pb, but interindividual differences in K2 have little influence on the overall rate constant for elimination of Pr.