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[1]程俊霖,刘江慧,胡云芳,等.DPPⅣ抑制剂对2型糖尿病的Ⅰ期临床研究[J].医学研究与战创伤救治(原医学研究生学报),2014,16(06):592-596.[doi:10.3969/j.issn.1672-271X.2014.06.010]
　CHENG Jun-lin,LIU Jiang-hui,HU Yun-fang,et al.Phase Ⅰ clinical study in a dipeptidyl peptidase Ⅳ inhibitor treatment of diabetes in type 2 diabetic patients[J].JOURNAL OF MEDICALRESEARCH —COMBAT TRAUMA CARE,2014,16(06):592-596.[doi:10.3969/j.issn.1672-271X.2014.06.010]
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DPPⅣ抑制剂对2型糖尿病的Ⅰ期临床研究()
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《医学研究与战创伤救治》（原医学研究生学报）[ISSN:1672-271X/CN:32-1713/R]

卷:
第16卷
期数:
2014年06期
页码:
592-596
栏目:
出版日期:
2014-11-20

文章信息/Info

Title:
Phase Ⅰ clinical study in a dipeptidyl peptidase Ⅳ inhibitor treatment of diabetes in type 2 diabetic patients
作者:
程俊霖; 刘江慧; 胡云芳; 于翠霞; 樊宏伟
210012 江苏南京，南京医科大学附属南京医院(南京市第一医院)临床药理实验室
Author(s):
CHENG Jun-lin; LIU Jiang-hui; HU Yun-fang; YU Cui-xia; FAN Hong-wei.
Department of Clinical Pharmacology，Nanjing First Hospital，Nanjing Medical University， Nanjing，Jiangsu 210012，China
关键词:
二肽基肽酶Ⅳ抑制剂; 安全性; 药代动力学; 药效动力学
Keywords:
DPPⅣ inhibitor;  safety;  pharmacokinetics;  pharmacodynamics
分类号:
R969;R781
DOI:
10.3969/j.issn.1672-271X.2014.06.010
文献标志码:
A
摘要:
目的 评价某二肽基肽酶Ⅳ(dipeptidyl peptldase Ⅳ，DPPⅣ)抑制剂连续多次口服给药的安全性，同时进行药代/药效动力学研究。方法 用随机、安慰剂平行对照、双 盲、多剂量递增给药的多中心临床试验方法，将36名2型糖尿病受试者随机纳入DPPⅣ抑制剂50 mg组、100 mg组、200 mg组；每组12例受试者中，10例接受DPPⅣ抑制剂，2例接受安 慰剂。试验疗程为7 d，以葡萄糖、胰岛素、C肽在空腹、餐后3 h、口服葡萄糖耐量试验(oral glucose tolerance test，OGTT)的相应指标即0-3h的曲线下面积(AUC0-3h)为药效指 标，评价此DPPⅣ抑制剂及其代谢产物浓度与胰高血糖素样肽1(glucagon-like peptide 1，GLP-1)的关系，分析其耐受性和安全性。结果 揭盲后对3个剂量组和安慰剂组共4组进行 分析。安慰剂组与各剂量DPPⅣ抑制剂组均无严重不良事件和重要医学事件发生。给药7d后50 mg组空腹血糖以及100 mg组的空腹血糖、餐后3 h血糖以及OGTT后AUC0-3h均有显著降 低(P＜0.05)。50 mg组的OGTT后胰岛素AUC0-3h升高、100 mg组的餐后3 h胰岛素水平升高以及50 mg组餐后3 h的C肽升高、200 mg组的OGTT后C肽AUC0-3h均显著升高(P＜0.05)。当 药物剂量在50、100、200 mg范围递增时，药物浓度先不变后增高，而餐后GLP-1水平先显著增高后不变。结论 此DPPⅣ抑制剂在2型糖尿病受试者中有较好的安全性和耐受性，推荐 100 mg为Ⅱ期临床试验剂量。
Abstract:
Objective To evaluate the safety and pharmacokinetics/pharmacodynamics of a new Dipeptidyl Peptidase Ⅳ (DPPⅣ) inhibitor with continuous administration of 7 d in Type 2 diabetes patients.Methods A randomized,placebo controlled,double-blinded,increasing multi-dosage,multi-center clinical research were performed.36 of type 2 diabetes patients were included in 50 mg,100 mg,200 mg groups in time sequence.In each group,10 cases accept the DPPⅣ inhibitor and 2 cases received placebo control.After 7d administration of the drug,glucose,insulin and c-peptide of fasting,postprandial 3 h and AUC0-3h were detected.The relationship of drug concentration and GLP-1 was analyzed.Results Data were analyzed by drug groups and the placebo group (n=4) after unblinding.The incidence of adverse events between drug groups and placebo was no significant difference.The reduced fasting blood glucose in 50 mg group,decreased fasting glucose,3 h postprandial blood glucose and glucose of AUC0-3h after OGTT in 100 mg were significantly lower (P＜0.05).Both increased 3 h postprandial insulin in 100 mg group and AUC0-3h after OGTT in 50 mg group and fasting C-peptide in 50 mg group,AUC0-3h of C-peptide in 50 and 200 mg groups increased significantly (P＜0.05).AUC0-3h of GLP-1 increased sharply then retained while the drug concentration retained then increased as dosage ranged from 50 mg to 200 mg.Conclusion The DPPⅣ inhibitor is safe in type 2 diabetes patients and 100 mg is recommended in phase Ⅱ clinical trials.

参考文献/References:

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备注/Memo

备注/Memo:
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更新日期/Last Update: 2014-11-20