Effects of age and gender on single-dose pharmacokinetics of gabapentin

Purpose: This study was conducted to evaluate the effect of age, age-related changes in renal function, and gender on the single-dose pharmacokinetics of orally administered gabapentin (GBP). Methods: The pharmacokinetics of a single 400-mg oral dose of GBP were studied in 36 healthy subjects (18 men and 18 women) aged 20-78 years. Serial blood samples and total urine output were collected for 48 h after the dose. GBP concentrations in plasma and urine were measured by high-performance liquid chromatography, and pharmacokinetic parameters were calculated by noncompartmental methods. Results: All subjects tolerated the drug well, with only mild symptoms reported. No change in maximal GBP plasma concentration (C-max), time at which C-max occurred (t(max)), Or apparent volume of distribution (V/F) with age was noted. A significant linear decline in apparent oral clearance (CL/F), elimination-rate constant (lambda(z)), and renal clearance (CLR) with increasing age was observed (p < 0.005). Because total urinary recovery of unchanged drug (an estimate of F for GBP) did not change with age, the decline in CL/F and lambda(z) can be explained by the decline in CLR. The only pbarmacokinetic parameter that was significantly different between genders was C-max, which was similar to 25% higher for women than for men (p = 0.016), consistent with gender differences in body size. Conclusions: The results of this study suggest that changes in renal function are responsible for age-related changes in GBP pharmacokinetics. Reduction of GBP dosage may be required in elderly patients with reduced renal function. The pharmacokinetics of GBP are similar in men and women.