Nonlinear Pharmacokinetics of CI-912 in Adult Epileptic Patients

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Abstract
The pharmacokinetics of CI-912 (1,2-benzisoxazole-3-methanesulfonamide) were studied in 10 adults with refractory partial seizures, during an open-label pilot study. Plasma and whole blood concentrations were measured by a high-performance liquid chromatographic method after a single dose and up to, and at steady-state with, 1 or 2 dosage regimens. Steady-state clearances averaged only 42% (range 20-60%) of single-dose clearances. Vm and Km values of the Michaelis-Menten equation were calculated for 9 of the 10 patients by a new method: Vm averaged 1272 (range 500-1973) mg/day and Km averaged 25.1 (range 9.23-52.5) .mu.g/ml. The best initial dosage for a new patient is 300 mg CI-912 every 12 h.