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- Title
Clinical Pharmacokinetics of XP13512, a Novel Transported Prodrug of Gabapentin.
- Authors
Cundy, Kenneth C.; Sastry, Srikonda; Wendy Luo; Joan Zou; Moors, Tristen L.; Canafax, Daniel M.
- Abstract
Gabapentin absorption occurs in only a limited region of the small intestine and saturates at doses used clinically, resulting in dose-dependent pharmacokinetics, high interpatient variability, and potentially ineffective drug exposure. XP13512/GSK1838262 is a novel transported prodrug of gabapentin that is absorbed throughout the entire length of the intestine by high-capacity nutrient transporters. 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%). XP13512 may therefore provide more predictable gabapentin exposure and decreased dosing frequency.
- Subjects
PHARMACOKINETICS; BIOCHEMISTRY; PRODRUGS; ANTIBODY-directed enzyme prodrug therapy; PHARMACOLOGY
- Publication
Journal of Clinical Pharmacology, 2008, Vol 48, Issue 12, p1378
- ISSN
0091-2700
- Publication type
Article
- DOI
10.1177/0091270008322909