Gabapentin is approved for the treatment of postherpetic neuralgia (PHN) and epilepsy. The pharmacokinetic
(PK) properties of gabapentin, including absorption, distribution, metabolism, and excretion (ADME), were investigated
during the development of Neurontin®, an immediate-release (IR) formulation of gabapentin that is orally administered
three-times daily. Recently, a gastroretentive (GR) once-daily formulation of gabapentin (Gralise®) has been developed
and marketed for the treatment of PHN.
This review focuses on the ADME properties of gabapentin and illustrates how GR delivery enhances its absorption
compared with IR formulations and allows once-daily dosing with the evening meal for the treatment of PHN. It includes
the following aspects: 1) the mechanism of gastroretention of gabapentin GR tablets, 2) in vitro dissolution profiles of the
GR and IR formulations, 3) site of absorption of gabapentin in the human intestine, 4) studies of the mechanism of
gabapentin absorption using intestinal tissue preparations, 5) human PK studies to examine the effects of dose and
formulations on PK profiles and the bioavailability of gabapentin at therapeutically relevant doses, and 6) efficacy and
safety of gastroretentive gabapentin in patients with PHN.
The data reviewed support that GR delivery of gabapentin optimizes its absorption via a saturable uptake mechanism. The
prolonged residence of the GR tablets in the stomach coupled with the gradual release of gabapentin attenuates saturation
of the transporter, thus enhancing absorption and increasing bioavailability, especially at therapeutically relevant doses.
The net result is a once-daily formulation of gabapentin that is well tolerated and efficacious for the treatment of PHN.