Pharmacokinetics of gabapentin in subjects with various degrees of renal function.
The pharmacokinetics of oral gabapentin (400 mg) was studied in normal subjects and in subjects with various degrees of renal function. Sixty subjects participated in this three-center study. None of the subjects were receiving hemodialysis. Plasma and urine samples were collected for up to 264 hours after dosing, and concentrations of gabapentin were determined by high performance liquid chromatography. Apparent oral plasma clearance (CL/F) and renal clearance (CLR) of gabapentin decreased and maximum plasma concentration, time to reach maximum concentration, and half-life values increased as renal function diminished. Gabapentin CL/F and CLR were linearly correlated with creatinine clearance. Total urinary recovery of unchanged drug was comparable in all subjects, indicating that the extent of drug absorption was unaffected by renal function. There was no evidence of gabapentin metabolism even in subjects with severe renal impairment. In summary, impaired renal function results in higher plasma gabapentin concentrations, longer elimination half-lives, and reduced CL/F and CLR values. Based on pharmacokinetic considerations, it appears that the dosing regimen of gabapentin in subjects with renal impairment may be adjusted on the basis of creatinine clearance.
Blum
R A
RA
Clinical Pharmacokinetics Laboratory, Millard Fillmore Hospital, Buffalo, NY 14209.
Comstock
T J
TJ
Sica
D A
DA
Schultz
R W
RW
Keller
E
E
Reetze
P
P
Bockbrader
H
H
Tuerck
D
D
Busch
J A
JA
Reece
P A
PA
D000085:Acetates / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000588:Amines; D003404:Creatinine / Q000097:blood / Q000652:urine; D003509:Cyclohexanecarboxylic Acids; D005260:Female; D000077206:Gabapentin; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D051437:Renal Insufficiency / Q000097:blood / Q000378:metabolism* / Q000652:urine; D005680:gamma-Aminobutyric Acid
D000085:Acetates; D000588:Amines; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D003404:Creatinine