Inter- and intra-subject variability in gabapentin absorption and absolute bioavailability

XP13512 [(±)-1-([(α-Isobutanoyloxyethoxy)carbonyl] aminomethyl)-1-cyclohexane Acetic Acid], A Novel Gabapentin Prodrug: I. Design, Synthesis, Enzymatic Conversion to Gabapentin, and Transport by Intestinal Solute Transporters

“…The absorption pathway for gabapentin in human intestine can be saturated at doses that are used to treat neuropathic pain. As a result, plasma levels of gabapentin are unpredictable and may not reach therapeutically useful levels in some patients (Gidal et al, 2000). It has been reported recently that exposure to gabapentin at high oral doses increased in a linear manner (Berry et al, 2003).…”

“…The drug has also shown efficacy in the treatment of a variety of additional indications, including restless legs syndrome (Garcia-Borreguero et al, 2002), anxiety disorders (Pollack et al, 1998), hot flashes (Guttuso et al, 2003), diabetic neuropathy (Backonja et al, 1998), and other painful neuropathies. The clinical pharmacokinetics of gabapentin have been studied in healthy volunteers and patients with epilepsy (McLean, 1995;Gidal et al, 1998Gidal et al, , 2000Boyd et al, 1999).…”

XP13512 [(±)-1-([(α-Isobutanoyloxyethoxy)carbonyl] aminomethyl)-1-cyclohexane Acetic Acid], A Novel Gabapentin Prodrug: II. Improved Oral Bioavailability, Dose Proportionality, and Colonic Absorption Compared with Gabapentin in Rats and Monkeys

“…1) (Kelly, 1998). Its efficacy in neuropathic pain and epilepsy may involve binding of the drug to the ␣ 2 ␦ subunit of a voltage-dependent calcium channel (Gee et al, 1996;Marais et al, 2001).The clinical pharmacokinetics of gabapentin have been studied in healthy volunteers and patients with epilepsy (McLean, 1995;Gidal et al, 1998Gidal et al, , 2000Boyd et al, 1999). Gabapentin bioavailability is dose-dependent, decreasing from an average of about 60% at a 300-mg dose to about 35% or less at doses used to treat neuropathic pain.…”

A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Tolerability of Gabapentin Enacarbil in Subjects with Restless Legs Syndrome

“…13,14 Additionally, the short half-life of gabapentin requires frequent dosing. 13,15 Gabapentin enacarbil (GEn) is an actively transported prodrug of gabapentin that overcomes the pharmacokinetic limitations of gabapentin through absorption by high-capacity nutrient transporters located throughout the large and small intestine.…”