The Intestinal Absorption Mechanism of Gabapentin Makes it Appropriate for Gastroretentive Delivery

Title:The Intestinal Absorption Mechanism of Gabapentin Makes it Appropriate for Gastroretentive Delivery

Volume: 8 Issue: 1

Author(s): Cuiping Chen, Verne E. Cowles and Michael Sweeney

Affiliation:

Keywords: Drug transporter, gabapentin, gastroretentive delivery, immediate-release, oral absorption, pharmacokinetics, postherpetic neuralgia, enhanced bioavailability, plasma concentrations, intestine’s epithelium

Abstract: 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.

Cite this article as:

Chen Cuiping, E. Cowles Verne and Sweeney Michael, The Intestinal Absorption Mechanism of Gabapentin Makes it Appropriate for Gastroretentive Delivery, Current Clinical Pharmacology 2013; 8 (1) . https://dx.doi.org/10.2174/1574884711308010009