Gabapentin enacarbil

478296-72-9

C16H27NO6

H2O : < 0.1 mg/mL (insoluble)

Membrane Transporter/Ion Channel; Neuronal Signaling

Gabapentin enacarbil (XP-13512) is a prodrug for the anticonvulsant and analgesic drug gabapentin. IC50 Value: Target: Calcium Channel Gabapentin enacarbil is an actively transported prodrug of gabapentin that provides sustained dose-proportional exposure to gabapentin and predictable bioavailability. in vitro: The prodrug (XP-13512) demonstrated active apical to basolateral transport across Caco-2 cell monolayers and pH-dependent passive permeability across artificial membranes. XP13512 inhibited uptake of (14)C-lactate by human embryonic kidney cells expressing monocarboxylate transporter type-1, and direct uptake of prodrug by these cells was confirmed using liquid chromatography-tandem mass spectrometry. XP13512 inhibited uptake of (3)H-biotin into Chinese hamster ovary cells overexpressing human sodium-dependent multivitamin transporter (SMVT) [1]. in vivo: In 4 studies of healthy volunteers (136 subjects total), the pharmacokinetics of XP13512 immediate- and extended-release formulations were compared with those of oral gabapentin. XP13512 immediate-release (up to 2800 mg single dose and 2100 mg twice daily) was well absorbed (>68%, based on urinary recovery of gabapentin), converted rapidly to gabapentin, and provided dose-proportional exposure, whereas absorption of oral gabapentin declined with increasing doses to <27% at 1200 mg. Compared with 600 mg gabapentin, an equimolar XP13512 extended-release dose provided extended gabapentin exposure (time to maximum concentration, 8.4 vs 2.7 hours) and superior bioavailability (74.5% vs 36.6%) [2]. Toxicity: Gabapentin's most common side effects in adult patients include dizziness, fatigue, weight gain, drowsiness, and peripheral edema (swelling of extremities).