摘要
目的评价某二肽基肽酶Ⅳ(dipeptidyl peptldaseⅣ,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 peptide1,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。
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 DPPⅣinhibitor and 2 cases received placebo con-trol.After 7d administration of the drug,glucose,insulin and c-peptide of fasting,postprandial 3 h and AUC0-3h were detected.The rela-tionship of drug concentration and GLP-1 was analyzed.Results Data were analyzed by drug groups and the placebo group （n=4） af-ter 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 AUC 0-3h 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 DPPⅣinhibitor is safe in type 2 diabetes patients and 100 mg is recommended in phase Ⅱclinical trials.
出处
《东南国防医药》
2014年第6期592-596,共5页
Military Medical Journal of Southeast China
