Gabapentin enacarbil

Gabapentin enacarbil (XP-13512) is a prodrug of Gabapentin (HY-A0057) designed to be absorbed throughout the intestine by high-capacity nutrient transporters. Gabapentin is a potent, orally active P/Q type Ca²⁺ channel blocker. Gabapentin enacarbil can be used for the study of Restless Legs Syndrome (RLS) and postherpetic neuralgia (PHN)^[1][2]. In Vitro:Gabapentin enacarbil (XP-13512) demonstrates active apical to basolateral transport across Caco-2 cell monolayers and pH-dependent passive permeability across artificial membranes^[1].
Gabapentin enacarbil inhibits uptake of ¹⁴C-lactate by human embryonic kidney cells expressing monocarboxylate transporter type-1^[1].
Gabapentin enacarbil inhibits uptake of ³H-biotin into Chinese hamster ovary cells overexpressing human sodium-dependent multivitamin transporter (SMVT)^[1].
In Vivo:Gabapentin enacarbil (XP-13512) is stable at physiological pH but rapidly converted to gabapentin in intestinal and liver tissue from rats, dogs, monkeys, and humans^[1].
In rats, >95% of an oral dose of ¹⁴C-Gabapentin enacarbil is excreted in urine in 24 h as Gabapentin^[2].
In monkeys, oral bioavailability of Gabapentin from Gabapentin enacarbil capsules was 84.2%^[2].
Compared with intracolonic Gabapentin, intracolonic Gabapentin enacarbil gave a 17-fold higher Gabapentin exposure in rats and 34-fold higher in monkeys^[2].
Gabapentin enacarbil may therefore be incorporated into a sustained release formulation to provide extended Gabapentin exposure. Gabapentin enacarbil demonstrates improved Gabapentin bioavailability, increases dose proportionality, and enhances colonic absorption^[2].