胃动素激动剂卡米西明（GSK962040）对不耐受喂养的危重症患者胃排空和葡萄糖吸收的影响：一项随机、双盲、安慰剂对照临床试验。
The effect of camicinal (GSK962040), a motilin agonist, on gastric emptying and glucose absorption in feed-intolerant critically ill patients: a randomized, blinded, placebo-controlled, clinical trial.
作者信息
Chapman Marianne J, Deane Adam M, O'Connor Stephanie L, Nguyen Nam Q, Fraser Robert J L, Richards Duncan B, Hacquoil Kimberley E, Vasist Johnson Lakshmi S, Barton Matthew E, Dukes George E
机构信息
Department of Critical Care Services, Royal Adelaide Hospital, North Terrace, Adelaide, Australia.
Discipline of Acute Care Medicine, University of Adelaide, Adelaide, Australia.
出版信息
Crit Care. 2016 Aug 1;20(1):232. doi: 10.1186/s13054-016-1420-4.
BACKGROUND
The promotility agents currently available to treat gastroparesis and feed intolerance in the critically ill are limited by adverse effects. The aim of this study was to assess the pharmacodynamic effects and pharmacokinetics of single doses of the novel gastric promotility agent motilin agonist camicinal (GSK962040) in critically ill feed-intolerant patients.
METHODS
A prospective, randomized, double-blind, parallel-group, placebo-controlled, study was performed in mechanically ventilated feed-intolerant patients [median age 55 (19-84), 73 % male, APACHE II score 18 (5-37) with a gastric residual volume ≥200 mL]. Gastric emptying and glucose absorption were measured both pre- and post-treatment after intragastric administration of 50 mg (n = 15) camicinal and placebo (n = 8) using the (13)C-octanoic acid breath test (BTt1/2), acetaminophen concentrations, and 3-O-methyl glucose concentrations respectively.
RESULTS
Following 50 mg enteral camicinal, there was a trend to accelerated gastric emptying [adjusted geometric means: pre-treatment BTt1/2 117 minutes vs. post- treatment 76 minutes; 95 % confidence intervals (CI; 0.39, 1.08) and increased glucose absorption (AUC240min pre-treatment: 28.63 mmol.min/L vs. post-treatment: 71.63 mmol.min/L; 95 % CI (1.68, 3.72)]. When two patients who did not have detectable plasma concentrations of camicinal were excluded from analysis, camicinal accelerated gastric emptying (adjusted geometric means: pre-treatment BTt1/2 121 minutes vs. post-treatment 65 minutes 95 % CI (0.32, 0.91) and increased glucose absorption (AUC240min pre-treatment: 33.04 mmol.min/L vs. post-treatment: 74.59 mmol.min/L; 95 % CI (1.478, 3.449). In those patients receiving placebo gastric emptying was similar pre- and post-treatment.
CONCLUSIONS
When absorbed, a single enteral dose of camicinal (50 mg) accelerates gastric emptying and increases glucose absorption in feed-intolerant critically ill patients.
TRIAL REGISTRATION
The study protocol was registered with the US NIH clinicaltrials.gov on 23 December 2009 (Identifier NCT01039805 ).
背景
目前用于治疗危重症患者胃轻瘫和喂养不耐受的促动力药物存在不良反应限制。本研究旨在评估新型胃促动力药物胃动素激动剂卡米西平（GSK962040）单剂量给药对危重症喂养不耐受患者的药效学作用和药代动力学。
方法
对机械通气的喂养不耐受患者[中位年龄55岁（19 - 84岁），73%为男性，急性生理与慢性健康状况评分系统II（APACHE II）评分为18分（5 - 37分），胃残余量≥200 mL]进行一项前瞻性、随机、双盲、平行组、安慰剂对照研究。分别使用（13）C - 辛酸呼气试验（BTt1/2）、对乙酰氨基酚浓度和3 - O - 甲基葡萄糖浓度，在胃内给予50 mg卡米西平（n = 15）和安慰剂（n = 8）前后测量胃排空和葡萄糖吸收情况。
结果
给予50 mg肠内卡米西平后，有胃排空加速的趋势[调整几何均数：治疗前BTt1/2为117分钟，治疗后为76分钟；95%置信区间（CI；0.39，1.08）]以及葡萄糖吸收增加（治疗前240分钟曲线下面积：28.63 mmol·min/L，治疗后：71.63 mmol·min/L；95% CI（1.68，3.72）]。当将两名未检测到卡米西平血浆浓度的患者排除在分析之外时，卡米西平加速了胃排空（调整几何均数：治疗前BTt1/2为121分钟，治疗后为65分钟，95% CI（0.32，0.91））并增加了葡萄糖吸收（治疗前240分钟曲线下面积：33.04 mmol·min/L，治疗后：74.59 mmol·min/L；95% CI（1.478，3.449））。在接受安慰剂的患者中，治疗前后胃排空情况相似。
结论
单剂量肠内给予卡米西平（50 mg）吸收后，可加速危重症喂养不耐受患者的胃排空并增加葡萄糖吸收。
试验注册
该研究方案于2009年12月23日在美国国立卫生研究院clinicaltrials.gov注册（标识符NCT01039805）。
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