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. Sixt y subjects participated in this three-center study. None of the subjec ts were receiving hemodialysis. Plasma and urine samples were collecte d for up to 264 hours after dosing, and concentrations of gabapentin w ere determined by high performance liquid chromatography. Apparent ora l plasma clearance (CL/F) and renal clearance (CIR) of gabapentin decr eased and maximum plasma concentration, time to reach maximum concentr ation, and half-life values increased as renal function diminished. Ga bapentin CL/F and CL(R) were linearly correlated with creatinine clear ance. Total urinary recovery of unchanged drug was comparable in all s ubjects, 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 el imination half-lives, and reduced CL/F and CL(R) values. Based on phar macokinetic considerations, it appears that the dosing regimen of gaba pentin in subjects with renal impairment may be adjusted on the basis of creatinine clearance.