Abstracts

RATIONALE: The objective of this study was to determine if co-administration of valproate (VPA) under steady state conditions alters the absorption or metabolism of levetiracetam (LEV) or excretion of LEV and ucb L057 (LEV metabolite). METHODS: 16 healthy, drug-free volunteers (10 male, 6 female 19-55 years of age) were studied. Single oral doses of 1500 mg of LEV were administered on days 1 and 10. VPA was administered orally at a rate of 500 mg/d from days 3 to 11. Blood and urine were collected for 48 hrs after each LEV dose for calculation of the following pharmacokinetic parameters of LEV and ucb L057: Apparent plasma clearance in ml/min/kg (CL), Area Under Curve in g.h/mL (AUC), elimination rate constant in L/hr (?z), volume of distribution in L/kg (VD) 48 hr relative urinary excretion in % of the dose (FE). RESULTS: The following results were obtained for LEV (mean ?SD; day 1, day 10): CL 0.89?0.11, 0.90?0.13; AUC 400?47, 397?60; ?z 0.095?0.014, 0.094?0.012; VD 0.57?0.07, 0.58?0.08; FE 62.6?5.7, 58.1?7.6. The following results were obtained for ucb L057 (mean?SD; day 1, day 10): AUC 23.0?6.5, 21.9?6.3; ?z 0.082?0.011, 0.082?0.011; FE 20.5?5.0, 18.3?3.9. The ratio of the geometric means for AUCs (90% confidence interval) was 98.9% (96.2; 101.6) for LEV and 95.0% (90.3; 99.9) for ucb L057. The average plasma concentrations of VPA at day 10 were 72.5?16.6 g/mL. CONCLUSIONS: Co-administration of VPA did not alter the pharmacokinetics or urinary excretion of LEV or ucb L057. Because the 48 hr excretion of LEV and ucb L057 did not change in the presence VPA, one can conclude the extent of oral absorption, the metabolism and urinary excretion of LEV were not altered by the presence of VPA.