Effects of age and gender on single-dose pharmacokinetics of gabapentin.
OBJECTIVE
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 (Cmax), time at which Cmax occurred (tmax), 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 pharmacokinetic parameter that was significantly different between genders was Cmax, which was approximately 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.
Boyd
R A
RA
Department of Pharmacokinetics, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, Michigan, USA.
Türck
D
D
Abel
R B
RB
Sedman
A J
AJ
Bockbrader
H N
HN
D000085:Acetates / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000284:Administration, Oral; D000328:Adult; D017677:Age Distribution; D000367:Age Factors; D000368:Aged; D000588:Amines; D000927:Anticonvulsants / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001824:Body Constitution; D003509:Cyclohexanecarboxylic Acids; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D000077206:Gabapentin; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D012737:Sex Factors; D005680:gamma-Aminobutyric Acid
D000085:Acetates; D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin