Pharmacokinetic and pharmacodynamic interaction of DWP16001, a sodium-glucose cotransporter-2 inhibitor, with phentermine in healthy subjects.

IF 3.9 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Expert Opinion on Drug Metabolism & Toxicology Pub Date : 2023-07-01 Epub Date: 2023-08-25 DOI:10.1080/17425255.2023.2249397

Sukyong Yoon, Min Soo Park, Byung Hak Jin, Hyobin Shin, Jaejin Na, Wan Huh, Choon Ok Kim

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Abstract

Background: DWP16001, a sodium-glucose cotransporter-2 inhibitor, has shown promise for improving blood glucose control and facilitating weight loss. Co-administration with phentermine could enhance these effects. So, we aimed to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) interactions of DWP16001 and phentermine.

Methods: We conducted a randomized, open-label, 3-treatment, 6-sequence, 3-period crossover study involving 24 healthy adults. Participants received either DWP16001 (2 mg), phentermine (37.5 mg), or a combination of both once daily for 7 days. Blood samples, urine samples, and body weights were collected to evaluate the PK and PD.

Results: The PK of the combination was found to be similar to that of the monotherapy. The geometric mean ratio (GMR) of C_max,ss, and AUC_tau,ss were 0.98 and 1.00, respectively, for DWP16001, and 1.01 and 0.94, respectively, for phentermine. Co-administration did not significantly affect the 24-hour urinary glucose excretion compared to DWP16001 monotherapy, and the GMR was 0.90. Participants tended to experience greater weight loss in the combination therapy group, and all demonstrated good tolerance.

Conclusions: Our findings indicate that there were no significant interactions during co-administration. These results suggest that the combination of DWP16001 and phentermine may be safe and effective for the treatment of obesity and diabetes.

Clinical trial registration: NCT05321732.

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钠-葡萄糖协同转运蛋白2抑制剂DWP16001与苯妥明在健康受试者中的药代动力学和药效学相互作用。

背景：DWP16001，一种钠-葡萄糖协同转运蛋白2抑制剂，已显示出改善血糖控制和促进减肥的前景。与芬特明联合给药可以增强这些作用。因此，我们旨在评估DWP16001和苯妥明的药代动力学（PK）和药效学（PD）相互作用。方法：我们对24名健康成年人进行了一项随机、开放标签、3治疗、6序列、3周期的交叉研究。参与者收到DWP16001（2 mg），苯妥明（37.5 mg），或两者的组合，每天一次，持续7 天。采集血样、尿样和体重以评估PK和PD。结果：发现联合用药的PK与单药治疗的PK相似。DWP16001的Cmax，ss和AUCtau，ss的几何平均比（GMR）分别为0.98和1.00，芬特明分别为1.01和0.94。与DWP16001单药治疗相比，联合用药对24小时尿糖排泄没有显著影响，GMR为0.90。联合治疗组的参与者往往会经历更大的体重减轻，并且都表现出良好的耐受性。结论：我们的研究结果表明，在联合给药期间没有显著的相互作用。这些结果表明，DWP16001和芬特明联合治疗肥胖和糖尿病可能是安全有效的。临床试验注册号：NCT05321732。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Expert Opinion on Drug Metabolism & Toxicology 医学-生化与分子生物学

CiteScore

7.90

自引率

2.30%

发文量

审稿时长

4-8 weeks

期刊介绍： Expert Opinion on Drug Metabolism & Toxicology (ISSN 1742-5255 [print], 1744-7607 [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles on all aspects of ADME-Tox. Each article is structured to incorporate the author’s own expert opinion on the scope for future development. The Editors welcome: Reviews covering metabolic, pharmacokinetic and toxicological issues relating to specific drugs, drug-drug interactions, drug classes or their use in specific populations; issues relating to enzymes involved in the metabolism, disposition and excretion of drugs; techniques involved in the study of drug metabolism and toxicology; novel technologies for obtaining ADME-Tox data. Drug Evaluations reviewing the clinical, toxicological and pharmacokinetic data on a particular drug. The audience consists of scientists and managers in the pharmaceutical industry, pharmacologists, clinical toxicologists and related professionals.