Depomed, 1360 O'Brien Drive, Menlo Park, CA 94025, USA.
J Clin Pharmacol. 2011 Mar;51(3):346-58. doi: 10.1177/0091270010368411. Epub 2010 May 19.
The objectives of the 3 phase I studies described herein were (1) to compare the pharmacokinetics of gabapentin delivered from a novel gastric-retentive dosage form vs an immediate-release formulation, (2) to assess the dose proportionality of the gastric-retentive extended-release formulation, and (3) to determine the effect of food on the pharmacokinetics of gabapentin delivered from this formulation. The time to reach maximum plasma concentration (t(max)) was extended for gabapentin delivered from the gastric-retentive extended-release formulation compared with the immediate-release formulation. A dose-related increase in both the maximum plasma concentration (C(max)) and the area under the plasma concentration-time curve (AUC) was observed as the gabapentin dose increased from 600 to 2400 mg. Fed status and increased fat content delayed t(max) and enhanced C(max) and AUC in proportion to the fat content. The pharmacokinetics of gabapentin delivered from this extended-release formulation allows a reduced dosing frequency while maintaining bioavailability and possibly diminishing the occurrence of adverse events attributable to a slower increase to the peak concentration compared with the immediate-release dosage form.
本文描述的 3 项 I 期研究的目的是：(1) 比较新型胃滞留剂型与速释制剂的加巴喷丁药代动力学；(2) 评估胃滞留型延长释放制剂的剂量比例；(3) 确定食物对该制剂中加巴喷丁药代动力学的影响。与速释制剂相比，胃滞留型延长释放制剂的达峰时间（t(max)）延长。随着加巴喷丁剂量从 600mg 增加到 2400mg，最大血浆浓度（C(max)）和血浆浓度-时间曲线下面积（AUC）均呈剂量相关性增加。进食状态和脂肪含量的增加使 t(max)延迟，C(max)和 AUC 按脂肪含量成比例增加。与速释剂型相比，这种延长释放制剂的加巴喷丁药代动力学允许减少给药频率，同时保持生物利用度，并可能减少与峰值浓度缓慢增加相关的不良反应的发生。
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