Pharmacokinetics and Pharmacodynamics of Prusogliptin (DBPR108), a Once-Daily Dipeptidyl Peptidase-4 Inhibitor, in Patients with Type 2 Diabetes.

IF 4 2区医学 Q1 PHARMACOLOGY & PHARMACY

Clinical Pharmacokinetics Pub Date : 2025-05-01 Epub Date: 2025-04-19 DOI:10.1007/s40262-025-01501-8

Wenfang Liu, Kexu Yang, Yang Lin, Chunyan Lu, Jingyi Liu, Huan Zhou, Juan Wang, Tianhao Zhang, Lingli Yao, Huanhuan Qi, Xiaofang Zhang, Rui Jia, Xiaoli Li, Shan Jing

{"title":"Pharmacokinetics and Pharmacodynamics of Prusogliptin (DBPR108), a Once-Daily Dipeptidyl Peptidase-4 Inhibitor, in Patients with Type 2 Diabetes.","authors":"Wenfang Liu, Kexu Yang, Yang Lin, Chunyan Lu, Jingyi Liu, Huan Zhou, Juan Wang, Tianhao Zhang, Lingli Yao, Huanhuan Qi, Xiaofang Zhang, Rui Jia, Xiaoli Li, Shan Jing","doi":"10.1007/s40262-025-01501-8","DOIUrl":null,"url":null,"abstract":"Background and objective: DBPR108 (prusogliptin) is a novel, orally bioavailable dipeptidyl peptidase-4 (DPP-4) inhibitor. This study investigated the pharmacokinetics and pharmacodynamic characteristics of DBPR108 tablets in patients with type 2 diabetes.Methods: In this randomized, parallel-group, open-label, phase I study, Chinese adults with type 2 diabetes, glycated hemoglobin of 7.0-9.5%, and body mass index of 19-35 kg/m2 were randomized 1:1:1 to once-daily DBPR108 50-, 100-, or 200-mg tablet groups. The primary endpoints included pharmacokinetic and pharmacodynamic characteristics after a single dose and multiple doses of DBPR108.Results: In total, 30 patients were randomized with 10 patients in each group. DBPR108 was quickly absorbed with median time to reach the maximum plasma concentration of 1.5-4 h at steady state. Exposure to DBPR108 at steady-state increased dose proportionally with mean maximum steady-state plasma DBPR108 concentration during dosage intervals of 119, 256, and 567 ng/mL in the 50-, 100-, and 200-mg groups, respectively. Accumulation ratio of DBPR108 ranged from 0.85 to 1.3, and steady state was reached after four continuous daily doses. After multiple doses of DBPR108, maximum inhibitory efficacy of DPP-4 increased with higher dose levels ranging from 62.1 to 89.4%. Active glucagon-like peptide-1 levels increased after DBPR108 administration. In addition, six patients experienced treatment-emergent adverse events without leading to treatment interruption or discontinuation.Conclusions: DBPR108 was well tolerated in Chinese patients with type 2 diabetes, and both the pharmacokinetic and pharmacodynamic profiles support once-daily dosage regimens of DBPR108 in future studies.Trial registration: ClinicalTrials.gov (NCT05146869); registered 23 November 2021.","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":"64 5","pages":"703-713"},"PeriodicalIF":4.0000,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12064631/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Pharmacokinetics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s40262-025-01501-8","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/4/19 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}

引用次数: 0

Abstract

Background and objective: DBPR108 (prusogliptin) is a novel, orally bioavailable dipeptidyl peptidase-4 (DPP-4) inhibitor. This study investigated the pharmacokinetics and pharmacodynamic characteristics of DBPR108 tablets in patients with type 2 diabetes.

Methods: In this randomized, parallel-group, open-label, phase I study, Chinese adults with type 2 diabetes, glycated hemoglobin of 7.0-9.5%, and body mass index of 19-35 kg/m² were randomized 1:1:1 to once-daily DBPR108 50-, 100-, or 200-mg tablet groups. The primary endpoints included pharmacokinetic and pharmacodynamic characteristics after a single dose and multiple doses of DBPR108.

Results: In total, 30 patients were randomized with 10 patients in each group. DBPR108 was quickly absorbed with median time to reach the maximum plasma concentration of 1.5-4 h at steady state. Exposure to DBPR108 at steady-state increased dose proportionally with mean maximum steady-state plasma DBPR108 concentration during dosage intervals of 119, 256, and 567 ng/mL in the 50-, 100-, and 200-mg groups, respectively. Accumulation ratio of DBPR108 ranged from 0.85 to 1.3, and steady state was reached after four continuous daily doses. After multiple doses of DBPR108, maximum inhibitory efficacy of DPP-4 increased with higher dose levels ranging from 62.1 to 89.4%. Active glucagon-like peptide-1 levels increased after DBPR108 administration. In addition, six patients experienced treatment-emergent adverse events without leading to treatment interruption or discontinuation.

Conclusions: DBPR108 was well tolerated in Chinese patients with type 2 diabetes, and both the pharmacokinetic and pharmacodynamic profiles support once-daily dosage regimens of DBPR108 in future studies.

Trial registration: ClinicalTrials.gov (NCT05146869); registered 23 November 2021.

查看原文本刊更多论文

每日一次的二肽基肽酶-4抑制剂普格列汀（DBPR108）在2型糖尿病患者中的药代动力学和药效学

背景与目的：DBPR108 （prusogliptin）是一种新型的口服生物可利用的二肽基肽酶-4 （DPP-4）抑制剂。本研究探讨了DBPR108片在2型糖尿病患者中的药代动力学和药效学特征。方法：在这项随机、平行组、开放标签的I期研究中，2型糖尿病、糖化血红蛋白7.0-9.5%、体重指数19-35 kg/m2的中国成年人按1:1:1随机分为每日一次的DBPR108 50、100或200 mg片剂组。主要终点包括单剂量和多剂量DBPR108后的药代动力学和药效学特征。结果：共30例患者随机分组，每组10例。DBPR108被快速吸收，中位时间为1.5-4 h，稳态时达到最大血药浓度。在50、100和200 mg组中，DBPR108稳态暴露剂量分别与119、256和567 ng/mL剂量间隔期间的平均最大稳态血浆DBPR108浓度成比例地增加。DBPR108的积累比为0.85 ~ 1.3，连续4天给药后达到稳态。多次给药DBPR108后，DPP-4的最大抑制效能随剂量的增加而增加，从62.1%到89.4%不等。给药后活性胰高血糖素样肽-1水平升高。此外，6名患者经历了治疗出现的不良事件，但没有导致治疗中断或停止。结论：DBPR108在中国2型糖尿病患者中耐受性良好，药代动力学和药效学分析均支持DBPR108在未来研究中每日一次的给药方案。试验注册：ClinicalTrials.gov (NCT05146869)；注册于2021年11月23日。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Clinical Pharmacokinetics 医学-药学

CiteScore

8.80

自引率

4.40%

发文量

审稿时长

6-12 weeks

期刊介绍： Clinical Pharmacokinetics promotes the continuing development of clinical pharmacokinetics and pharmacodynamics for the improvement of drug therapy, and for furthering postgraduate education in clinical pharmacology and therapeutics. Pharmacokinetics, the study of drug disposition in the body, is an integral part of drug development and rational use. Knowledge and application of pharmacokinetic principles leads to accelerated drug development, cost effective drug use and a reduced frequency of adverse effects and drug interactions.