The pharmacodynamics, safety and pharmacokinetics of single doses of the motilin agonist, camicinal, in type 1 diabetes mellitus with slow gastric emptying
The pharmacodynamics, safety and pharmacokinetics of single doses of the motilin agonist, camicinal, in type 1 diabetes mellitus with slow gastric emptying
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DOI：
10.1111/bph.13475
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发表时间：
2016-06-01
影响因子：
7.3
通讯作者：
Dukes, George E.
中科院分区：
文献类型：
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作者：
Hellstrom, Per M.;Tack, Jan;Dukes, George E.
背景和结论在此，我们研究了在具有胃轻瘫症状的胃排空缓慢病史的1型糖尿病（T1 DM）患者中，单剂量卡美西那的药代动力学、药效学和安全性。患者接受安慰剂和三种可能剂量的camicinal（25、50或125 mg）中的两种的口服给药。胃排空（C-13-辛酸呼气试验）、药代动力学和安全性是主要结果。与安慰剂相比，单次给予125 mg camicinal后，胃半排空时间缩短了-95 min（95% CI：-156.8，-34.2）（52 vs. 147 min，P < 0.05），改善了65%。与安慰剂相比，观察到camicinal 25和50 mg组的胃半排空时间缩短（约39 min），两种剂量均减少27%（无统计学显著性）。在所有剂量下均证明了阳性的剂量-反应关系。空腹血糖水平不影响卡美西那对胃半排空时间的影响。高达125 mg的单次给药耐受性良好。Camicinal吸收良好，表现出线性和近似剂量成比例的药代动力学特征和明确的urisure-response关系与胃排空.CONCLUSIONS AND IMPLICATIONSCamicinal显着加速胃排空固体T1 DM患者后，单次口服剂量。Camicinal耐受性良好，在糖尿病患者中表现出与先前在健康志愿者中报告的药代动力学特征相似的药代动力学特征。
BACKGROUND AND PURPOSEHere we have investigated the pharmacokinetics, pharmacodynamics and safety of single doses of camicinal in type 1 diabetes mellitus (T1DM) patients with a history of slow gastric emptying with symptoms consistent with gastroparesis.EXPERIMENTAL APPROACHIn a randomized, double-blind, placebo-controlled, incomplete block, three-period, two-centre crossover study, patients received oral administration of placebo and two of the three possible doses of camicinal (25, 50 or 125 mg). Gastric emptying (C-13-octanoic acid breath test), pharmacokinetics and safety were primary outcomes.KEY RESULTSNine of the 10 patients enrolled completed the study. Gastric half-emptying time decreased by -95 min (95% CI: -156.8, -34.2) after a single dose of camicinal 125 mg compared with placebo (52 vs. 147 min, P < 0.05), representing a 65% improvement. A decrease of the gastric half-emptying time compared with placebo (approximately 39 min) was observed with camicinal 25 and 50 mg, representing a 27% reduction for both doses (not statistically significant). A positive exposure-response relationship was demonstrated across all doses. The effects of camicinal on gastric half-emptying time were not influenced by fasting glucose levels. Single doses up to 125 mg were well tolerated. Camicinal was well absorbed, exhibiting linear and approximately dose-proportional pharmacokinetic characteristics and a clear exposure-response relationship with gastric emptying.CONCLUSIONS AND IMPLICATIONSCamicinal significantly accelerated gastric emptying of solids in T1DM patients following administration of a single oral dose. Camicinal was well tolerated and exhibited similar pharmacokinetic characteristics in diabetic patients to those previously reported in healthy volunteers.