Primidone kinetics: Effects of concurrent drugs and duration of therapy

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Abstract
Primidone (PRM) kinetics was examined in 2 groups of adult seizure patients: 10 newly diagnosed in whom only PRM was used, the monotherapy (MT) group, and 9 in whom PRM was added to other antiepileptics, the combination therapy (CT) group. Time-concentration data wwere obtained after an initial dose of 250 mg and during subsequent steady-state periods. PRM elimination was slower (P < 0.05) after the initial dose in MT patients (half-life (t 1/2) = 15.2 h, apparent clearance = 35 ml/h per kg) than in CT patients (t 1/2 = 8.3 h, clearance = 51 ml/h per kg). PRM metabolites, phenobarbital and phenylethylmalonamide, appeared much earlier in CT patients. Continued PRM exposure in MT patients was accompanied by an increase in apparent clearance in 3 of 7 patients, but no change in 4 of 7. In 4 CT patients in whom other antiepileptics were withdrawn there was a decrease in apparent clearance (61.4 to 29.9 ml/h per kg) to rates in the range of MT patients. PRM kinetics is influenced by concurrent antiepileptic drugs and by duration of PRM therapy.

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