Nonlinear pharmacokinetics of CI-912 in adult epileptic patients.
We studied the pharmacokinetics of CI-912 (1,2-benziosoxazole-3-methanesulfonamide) 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 chromatograph method after a single dose and up to and at steady state with one or two 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 1,272 (range 500-1,973) mg/day and Km averaged 25.1 (range 9.23-52.5) micrograms/ml. The best initial dosage for a new patient is 300 mg CI-912 every 12 h.
D000328:Adult; D000927:Anticonvulsants / Q000097:blood / Q000378:metabolism*; D004827:Epilepsy / Q000097:blood* / Q000188:drug therapy; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010080:Oxazoles / Q000378:metabolism*; D010865:Pilot Projects; D000078305:Zonisamide
D000927:Anticonvulsants; D007555:Isoxazoles; D010080:Oxazoles; D000078305:Zonisamide