Results From a Randomized, Open-Label, Crossover Study Evaluating the Effect of the Aldosterone Synthase Inhibitor Baxdrostat on the Pharmacokinetics of Metformin in Healthy Human Subjects,American Journal of Cardiovascular Drugs

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Results From a Randomized, Open-Label, Crossover Study Evaluating the Effect of the Aldosterone Synthase Inhibitor Baxdrostat on the Pharmacokinetics of Metformin in Healthy Human Subjects
American Journal of Cardiovascular Drugs ( IF 2.8 ) Pub Date : 2023-02-15 , DOI: 10.1007/s40256-023-00572-x
Mason W Freeman ₁ , Mary Bond ₂ , Brian Murphy ₂ , James Hui ₁ , Jonathan Isaacsohn ₂

Affiliation

Background

Due to the high comorbidity of diabetes and hypertension, co-administration of metformin with anti-hypertensive drugs is likely. Baxdrostat is an aldosterone synthase inhibitor in development for the potential treatment of hypertension. In vitro data indicated that baxdrostat inhibits the multidrug and toxin extrusion 1 (MATE1) and MATE2-K renal transporters. Metformin is a MATE substrate, so this study assessed potential effects of baxdrostat on the pharmacokinetics of metformin.

Methods

Twenty-seven healthy volunteers received 1000 mg metformin alone and 1000 mg metformin in the presence of 10 mg baxdrostat in a randomized, crossover manner. Each treatment was separated by 10 or more days. Blood and urine samples were collected over a 3-day period after each treatment to measure plasma and urine concentrations of metformin. Safety was assessed by adverse events (AEs), physical examinations, electrocardiograms, vital signs, and clinical laboratory evaluations.

Results

There were no deaths, serious AEs, discontinuations due to treatment-emergent AEs, or noteworthy increases in AEs with either treatment, indicating that metformin and baxdrostat were well-tolerated when co-administered. Baxdrostat did not significantly affect plasma concentrations or renal clearance of metformin.

Conclusion

The results of this study suggest that diabetic patients with hypertension receiving both metformin and baxdrostat are unlikely to require dose adjustment.

Registration

ClinicalTrials.gov identifier no. NCT05526690.

Graphical Abstract

中文翻译：

评估醛固酮合酶抑制剂 Baxdrostat 对健康人体受试者二甲双胍药代动力学影响的随机、开放标签、交叉研究的结果

背景

由于糖尿病和高血压的高合并症，二甲双胍与抗高血压药物的共同给药是可能的。Baxdrostat 是一种醛固酮合成酶抑制剂，正在开发中用于治疗高血压。体外数据表明，baxdrostat 抑制多药和毒素排出 1 (MATE1) 和 MATE2-K 肾转运蛋白。二甲双胍是一种 MATE 底物，因此本研究评估了巴司他对二甲双胍药代动力学的潜在影响。