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普通狨猴体内二甲双胍和阿卡波糖的药代动力学评估。

Evaluation of the pharmacokinetics of metformin and acarbose in the common marmoset.

作者信息

Fernandez Elizabeth, Ross Corinna, Liang Hanyu, Javors Martin, Tardif Suzette, Salmon Adam B

机构信息

Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, TX, USA.

Geriatric Research, Education and Clinical Center, South Texas Veteran's Health Care System, San Antonio.

出版信息

Pathobiol Aging Age Relat Dis. 2019 Aug 22;9(1):1657756. doi: 10.1080/20010001.2019.1657756. eCollection 2019.

Abstract

Metformin has beneficial effects on several age-related diseases (e.g., diabetes, obesity, cancer) and extends lifespan in nematodes and mice. Acarbose, an FDA-approved agent for treating type 2 diabetes, prevents breakdown of complex carbohydrates. Both compounds have been suggested as potential anti-aging interventions and acarbose has been shown to extend mouse longevity by the Intervention Testing Program (ITP). One potential next step is to assess the effect of these interventions on healthspan and lifespan in non-human primates. The common marmoset () is a small new world monkey with a relatively short life span and small size, both valuable for the translation potential of this nonhuman primate species for the study of aging and chronic disease. However, the dosing and assessment of potential side effects of either metformin or acarbose in this species have yet to be assessed. This study evaluated the pharmacokinetics of two dosage levels each of metformin or acarbose (given separately) in two small groups of young marmosets (n = 5/group) treated for 24 h to define the pharmacokinetics of each drug. The ability to rapidly and reliably dose socially housed marmosets with an oral form of acarbose or metformin that is well tolerated indicates that this species is a reliable model for testing acarbose and metformin in a safe and efficient way in a long-term intervention.

摘要

二甲双胍对多种与年龄相关的疾病(如糖尿病、肥胖症、癌症)具有有益作用,并可延长线虫和小鼠的寿命。阿卡波糖是一种经美国食品药品监督管理局(FDA)批准用于治疗2型糖尿病的药物,可防止复合碳水化合物的分解。这两种化合物都被认为是潜在的抗衰老干预措施,并且阿卡波糖已被干预测试计划(ITP)证明可延长小鼠的寿命。下一步潜在的做法是评估这些干预措施对非人类灵长类动物健康寿命和寿命的影响。普通狨猴是一种新世界小型猴,寿命相对较短且体型较小,这对于该非人类灵长类物种在衰老和慢性病研究中的转化潜力而言都很有价值。然而,二甲双胍或阿卡波糖在该物种中的给药剂量及潜在副作用评估尚未进行。本研究评估了在两组接受治疗24小时的幼年狨猴(每组n = 5)中分别给予二甲双胍或阿卡波糖两种剂量水平时的药代动力学,以确定每种药物的药代动力学。能够以口服形式快速且可靠地对群居的狨猴给予阿卡波糖或二甲双胍,且耐受性良好,这表明该物种是在长期干预中以安全有效的方式测试阿卡波糖和二甲双胍的可靠模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0928/6719263/144ba1d1a615/ZPBA_A_1657756_F0001_OC.jpg

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