Clinical pharmacology of gabapentin
The bioavailability of gabapentin is not dose-proportional; it decreases as the dose increases. When gabapentin is given in 3 divided doses, at 900 mg per day the bioavailability is approximately 60%, but at 2400 mg per day it drops to 34% and at 4800 mg per day it is only 27%.
Distribution and metabolism
Gabapentin is not metabolized, and does not induce or inhibit hepatic metabolism. It is not bound to plasma proteins and displays linear pharmacokinetics at usual dosages. Consequently, drug-drug interactions are not an issue with gabapentin.
The half-life of gabapentin in otherwise healthy patients with epilepsy is generally 4 to 9 hours; therefore, it is usually given three times a day.
Because the elimination of gabapentin is entirely renal, patients with renal insufficiency usually need lower dosages and less frequent dosing.
In patients with normal renal function, steady state is reached after 1 to 2 days of taking a stable dose of gabapentin. The dose that a patient takes should not be increased until steady state has been reached (or some time later), so that the effects of the previous dosage can be assessed.