Clinical Pharmacokinetics of XP13512, a Novel Transported Prodrug of Gabapentin
Clinical Pharmacokinetics of XP13512, a Novel Transported Prodrug of Gabapentin
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DOI：
10.1177/0091270008322909
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发表时间：
2008-12-01
影响因子：
2.9
通讯作者：
Canafax, Daniel M.
中科院分区：
文献类型：
--
作者：
Cundy, Kenneth C.;Sastry, Srikonda;Canafax, Daniel M.
加巴喷丁吸收仅发生在小肠的有限区域，并在临床使用的剂量下饱和，导致剂量依赖性药代动力学、高患者间变异性和潜在的无效药物暴露。XP 13512/GSK 1838262是加巴喷丁的一种新型转运前药，通过高容量营养转运蛋白在整个肠道长度内吸收。在4项健康志愿者（共136名受试者）研究中，比较了XP 13512速释和缓释制剂与口服加巴喷丁的药代动力学。XP 13512速释剂（高达2800 mg单次给药和2100 mg每日两次）吸收良好（> 68%，基于加巴喷丁的尿液回收率），迅速转化为加巴喷丁，并提供剂量比例性暴露，而口服加巴喷丁的吸收随着剂量增加而下降，
Gabapentin absorption occurs in only a limited region of the small intestine and saturates at doses used clinically, resulting in dose-dependent pharmacokinetics, high inter-patient 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