Abstracts

RATIONALE: Levetiracetam (LEV) and its major metabolite ucb L057 are primarily excreted by the kidney. A study was conducted to evaluate the pharmacokinetics of LEV in subjects with end stage renal disease (ESRD) undergoing hemodialysis and to assess the dialyzability and dialysis clearance of LEV and its major metabolite ucb L057. METHODS:_ Single-dose pharmacokinetic profiles were obtained over 104 hours following a 500 mg dose from five anuric subjects. Plasma and dialysate samples were collected during the two dialysis sessions. Additional plasma samples were obtained between sessions. Hemodialysis clearance was calculated during both dialysis sessions and the pharmacokinetics of LEV were assessed during the non-hemodialysis periods. RESULTS: In ESRD, LEV absorption was rapid and complete. Clearance was similar to non-renal clearance in subjects with normal renal function, as was the volume of distribution. Key pharmacokinetic parameters were: Cmax = 15.5+3.5 g/mL, Tmax = 1.7+0.4 hours, T1/2 = 24.6+7.8 hours, AUC 517+253 g/mL/hr, CL/f = 18.2+7.2 mL/min/1.73m2, Vz/f = 0.50+0.10 L/kg. Dialyzer extraction efficiency was high, leading to removal of half of LEV during a 4-hour session (hemodialysis clearance 127.2 and 99.1 mL/min/1.73m2, for LEV and ucb L057). CONCLUSIONS: These data indicate the need for LEV dose adjustments for ESRD patients. A typical ESRD patient will receive 500-1000 mg/day on non-dialysis days, supplemented by 250-500 mg following dialysis sessions.