Disposition of Gabapentin in Anuric Subjects on Hemodialysis

Abstract

Gabapentin is an anticonvulsant drug, which in man is cleared solely by renal excretion and is not bound to plasma proteins. Because the clearance of gabapentin is dependent on renal function, the pharmacokinetics of gabapentin were investigated in anuric subjects maintained on hemodialysis. Plasma samples were obtained over an 8-day period after administration of single oral 400-mg doses of gabapentin. Pre- and post-dialyzer plasma samples and dialysate samples from quantitative collection of dialyzer effluent were obtained during hemodialysis sessions performed 2, 4, and 7 days after dosing. A mean (SD) maximum gabapentin plasma concentration of 6.0 (2.4) micrograms/mL was achieved at 4.7 (2.1) hours post-dose. The elimination half-life of gabapentin on non-hemodialysis days averaged 132 hours. Approximately 35% of the gabapentin dose was recovered in dialysate, and mean hemodialysis clearance of gabapentin was 142 (26) mL/min; approximately 93% of the dialyzer creatinine clearance. Gabapentin elimination half-life during hemodialysis was approximately 4 hours. Systemic plasma gabapentin concentrations increased approximately 30% during the first 2 hours after hemodialysis as a result of drug redistribution in the body. It is recommended that patients with end-stage renal disease maintained on hemodialysis receive an initial 300-mg to 400-mg gabapentin loading dose. Plasma gabapentin concentrations can be maintained by giving 200 to 300 mg of gabapentin after every 4 hours of hemodialysis.