Clinical pharmacokinetics of gabapentin.

Pharmacokinetic properties are important to consider in evaluating the usefulness of new antiepileptic drugs (AEDs). Gabapentin is a new, water-soluble, antiepileptic agent with properties of an amino acid. This drug is rapidly absorbed and exhibits dose-dependent bioavailability as a result of a saturable transport mechanism. Plasma concentrations are essentially proportional to dosages up to 1,800 mg daily, which is the highest dosage used in double-blind, placebo-controlled clinical trials. Gabapentin is not protein-bound. A high volume of distribution indicates greater concentration in tissue than in plasma. It is not metabolized and does not induce hepatic enzymes or inhibit metabolism of other antiepileptic drugs. As a result, metabolism-related factors do not necessitate dosage alterations of gabapentin and concomitant AEDs after prolonged therapy. The drug is excreted unchanged in urine; plasma clearance is linearly related to creatinine clearance; and dosage is readily adjusted based on renal function. The elimination half-life is approximately 5 to 9 hours. Consequently, three divided doses are usually required per day, but steady state is rapidly achieved. No significant interactions between gabapentin and standard antiepileptic drugs or oral contraceptives have been observed. These and other pharmacokinetic properties make gabapentin unique among available AEDs.