Gabapentin Metabolism

Gabapentin is not appreciably metabolized in humans and is excreted unchanged by the kidneys. 1

Pharmacokinetic Properties of Gabapentin

Gabapentin is absorbed via the L-amino acid transport system in the proximal small bowel 2
Bioavailability is dose-dependent and decreases as dose increases due to a saturable transport mechanism 1, 3
Bioavailability is approximately 60%, 47%, 34%, 33%, and 27% following 900 mg, 1200 mg, 2400 mg, 3600 mg, and 4800 mg/day given in 3 divided doses, respectively 1
Food has only a slight effect on absorption (14% increase in AUC and Cmax) 1

Less than 3% of gabapentin circulates bound to plasma protein 1, 4
The apparent volume of distribution is 58±6 L after intravenous administration 1
Cerebrospinal fluid concentrations are approximately 20% of corresponding plasma concentrations in patients with epilepsy 1

Gabapentin is not appreciably metabolized in humans 1, 3
All pharmacological actions following gabapentin administration are due to the activity of the parent compound 1
There is no evidence of gabapentin metabolism even in subjects with severe renal impairment 5
Unlike many other medications, gabapentin does not undergo hepatic metabolism via the cytochrome P450 enzyme system 3, 4

Gabapentin is eliminated from the systemic circulation by renal excretion as unchanged drug 1, 5
The elimination half-life is 5 to 7 hours and is unaltered by dose or following multiple dosing 1, 3
Gabapentin elimination rate constant, plasma clearance, and renal clearance are directly proportional to creatinine clearance 1, 5
Total urinary recovery of unchanged drug is comparable in all subjects, indicating that the extent of drug absorption is unaffected by renal function 5
Gabapentin can be removed from plasma by hemodialysis 1

Due to its renal elimination, dosage adjustment is necessary in patients with impaired renal function 1, 5
Dosing regimen in subjects with renal impairment may be adjusted based on creatinine clearance 5
In elderly patients and those with impaired renal function, gabapentin plasma clearance is reduced 1

Gabapentin does not induce hepatic enzymes or inhibit metabolism of other antiepileptic drugs 3, 4
No significant interactions between gabapentin and standard antiepileptic drugs or oral contraceptives have been observed 3, 4
Due to its lack of metabolism and minimal protein binding, gabapentin has fewer drug interactions compared to many other antiepileptic medications 3, 4

In pediatric subjects between 1 month and <5 years of age, approximately 30% lower exposure (AUC) was achieved compared to those 5 years of age and older 1
Apparent oral clearance (CL/F) of gabapentin decreased as age increased, from about 225 mL/min in those under 30 years of age to about 125 mL/min in those over 70 years of age 1
No significant gender differences in pharmacokinetic parameters have been observed 1
Pharmacokinetic differences due to race have not been studied but are not expected due to the primarily renal excretion of gabapentin 1