Pharmacokinetic and Pharmacodynamic Interaction of Metformin and Ojeok-san in Healthy Volunteers.

IF 5.1 2区医学 Q1 CHEMISTRY, MEDICINAL

Drug Design, Development and Therapy Pub Date : 2025-09-06 eCollection Date: 2025-01-01 DOI:10.2147/DDDT.S526915

Sooyoung Lee, Sumin Chae, Minji Kwon, Wang-Seob Shim, Kyung-Tae Lee, Sung-Vin Yim, Bo-Hyung Kim

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Abstract

Purpose: This study aimed to evaluate the pharmacokinetics and pharmacodynamics of metformin and Ojeok-san (OJS) co-administration to healthy volunteers compared to those with metformin alone.

Methods: This was an open-label, one-sequence, crossover study, with two 2-day hospitalization schedules lasting up to 14 days. Metformin was administered once daily on days 1 and 2. OJS was administered alone three times a day on days 3-7 and co-administered with metformin once a day on days 8 and 9. Plasma concentrations of metformin were measured using a validated LC-MS/MS method. To evaluate pharmacodynamics, oral glucose tolerance tests (OGTTs) were performed on days 1, 2, 8 and 9.

Results: Fifteen participants were enrolled. The coadministration decreased C_max (1757.7 to 1668.9 ng/mL) and AUC_last (10407.4 to 9901.1 ng·h/mL), compared to those with metformin alone. Geometric mean ratios (90% Confidence Interval) of C_max and AUC_last between the co-administration with OJS and metformin alone were 92.15% (82.79-102.57) and 94.57% (85.6-104.48), respectively. Co-administration with OJS did not significantly change the mean glucose level compared to that with metformin alone.

Conclusion: Co-administration with OJS decreased the plasma concentrations of metformin compared to that with metformin alone. However, the degree of decrease was not significant based on the geometric mean of the C_max and AUC_last. Considering the OGTT results, these changes in metformin concentration did not affect glucose concentration. In addition, there were no significant findings regarding safety profiles.

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二甲双胍和五角山在健康志愿者体内的药代动力学和药效学相互作用。

目的：本研究旨在评价二甲双胍和ojek -san （OJS）联合给药与单用二甲双胍相比在健康志愿者体内的药代动力学和药效学。方法：这是一项开放标签、单序列、交叉研究，两个2天住院计划持续长达14天。二甲双胍在第1天和第2天每天1次。OJS在第3-7天每天单独给药3次，在第8天和第9天与二甲双胍每天联合给药1次。采用经验证的LC-MS/MS方法测定血浆二甲双胍浓度。为了评估药效学，在第1、2、8和9天进行口服葡萄糖耐量试验（ogtt）。结果：15名受试者入组。与单用二甲双胍相比，联合用药降低Cmax （1757.7 ~ 1668.9 ng/mL）和AUClast （10407.4 ~ 9901.1 ng·h/mL）。OJS与单用二甲双胍的Cmax和AUClast的几何平均比值（90%置信区间）分别为92.15%（82.79 ~ 102.57）和94.57%（85.6 ~ 104.48）。与单用二甲双胍相比，与OJS联合用药没有显著改变平均血糖水平。结论：与单用二甲双胍相比，OJS联合用药可降低血浆二甲双胍浓度。然而，从Cmax和AUClast的几何平均值来看，下降的程度并不显著。考虑OGTT结果，二甲双胍浓度的这些变化并不影响葡萄糖浓度。此外，在安全性方面也没有显著的发现。

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

Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY

CiteScore

9.00

自引率

0.00%

发文量

382

审稿时长

>12 weeks

期刊介绍： Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.