CAJ | 학술논문

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。
목적：평개모이태기태매Ⅳ（ dipeptidyl peptldase Ⅳ，DPPⅣ）억제제련속다차구복급약적안전성，동시진행약대／약효동역학연구。방법용수궤、안위제평행대조、쌍맹、다제량체증급약적다중심림상시험방법，장36명2형당뇨병수시자수궤납입DPPⅣ억제제50 mg조、100 mg조、200 mg조；매조12례수시자중，10례접수DPPⅣ억제제，2례접수안위제。시험료정위7 d，이포도당、이도소、C태재공복、찬후3 h、구복포도당내량시험（ oral glucose tolerance test ，OGTT）적상응지표즉0－3h적곡선하면적（AUC0－3h）위약효지표，평개차DPPⅣ억제제급기대사산물농도여이고혈당소양태1（glucagon-like peptide 1，GLP-1）적관계，분석기내수성화안전성。결과게맹후대3개제량조화안위제조공4조진행분석。안위제조여각제량DPPⅣ억제제조균무엄중불량사건화중요의학사건발생。급약7d후50 mg조공복혈당이급100 mg조적공복혈당、찬후3 h혈당이급OGTT후AUC0－3h균유현저강저（ P＜0．05）。50 mg조적OGTT후이도소AUC0－3h승고、100 mg조적찬후3 h이도소수평승고이급50 mg조찬후3 h적C태승고、200 mg조적OGTT후C태AUC0－3h균현저승고（P＜0．05）。당약물제량재50、100、200 mg범위체증시，약물농도선불변후증고，이찬후GLP-1수평선현저증고후불변。결론차DPPⅣ억제제재2형당뇨병수시자중유교호적안전성화내수성，추천100 mg위Ⅱ기림상시험제량。
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.