Clinical development of a once-daily gastroretentive formulation of gabapentin for treatment of postherpetic neuralgia: an overview.

Gabapentin immediate-release formulations (G-IR) administered three times a day is an efficacious treatment for postherpetic neuralgia (PHN), but its potential benefits may not be fully realized due to tolerability issues as well as its pharmacokinetic (PK) properties such as its short half-life, and regional and saturable absorption in the proximal small intestine. The gastroretentive once-daily formulation of gabapentin (G-GR) allows for less frequent dosing while maintaining efficacy and may also reduce adverse events (AEs) associated with high plasma concentration of gabapentin occurring during the waking hours. G-GR slowly releases the drug from the tablet to the upper small intestine, where gabapentin is best absorbed, over approximately 10 h. This report reviews the development of the gastroretentive technology used in the once-daily formulation of gabapentin (G-GR), and describes the clinical development of G-GR from PK studies through the Phase III efficacy and safety studies, with comparisons made with G-IR. The technology takes advantage of the normal physiology of the stomach in the fed state to provide gastroretention, which in turn allows for gradual release of the active ingredient over several hours to the small intestine where gabapentin is best absorbed. The GR technology used in G-GR resulted in a decreased dosing frequency from three times per day for the IR product to once daily in the treatment of PHN, while maintaining the same efficacy with an apparent reduced incidence of AEs common to G-IR therapy.