Michaelis-Menten kinetics of stiripentol in normal humans

Michaelis-Menten kinetic parameters for stiripentol, and anticonvulsant, were assessed in six normal volunteers. Stiripentol was administered orally three times a day in dosage increments of 600, 1,200, and 1,800 mg/day for consecutive periods of 3, 4, and 7 days, respectively. Stiripentol steady-state levels at the three dosing rates increased more than proportionally with dose. The mean +/- SD oral clearance of stiripentol at 600 mg/day (1,090 +/- 624 L/day) was significantly greater (p less than 0.01) than at 1,200 (506 +/- 219 L/day) or 1,800 (405 +/- 151 L/day) mg/day. Average steady-state concentrations predicted from individually determined Vm and Km parameters were in good agreement with experimentally observed levels, indicating that the kinetics of stiripentol are of the Michaelis-Menten type. The mean Vm, Km, and Vm/Km ratio were 2,299 +/- 490 mg/day, 2.20 +/- 1.28 mg/L, and 1,241 +/- 837 L/day, respectively. Neuropsychological tests carried out before and after 14 days of stiripentol treatment showed a significant decline in verbal learning ability (p = 0.038) and a significant improvement in a test of memory and attention (p less than 0.01).