Format

Send to

Choose Destination
J Clin Pharmacol. 2008 Dec;48(12):1378-88. doi: 10.1177/0091270008322909. Epub 2008 Sep 30.

Clinical pharmacokinetics of XP13512, a novel transported prodrug of gabapentin.

Author information

1
XenoPort Inc, 3410 Central Expressway, Santa Clara, CA 95051, USA. kcundy@xenoport.com

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.

PMID:
18827074
DOI:
10.1177/0091270008322909
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center