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评估 Capromorelin 在食蟹猕猴中的安全性和疗效()。

Evaluating the Safety and Efficacy of Capromorelin in Rhesus Macaques ().

机构信息

Division of Animal Resources, Emory National primate Research Center, Atlanta, Georgia.

Department of Biostatistics and Bioinformatics of the Rollins School of Public Health at Emory University, Atlanta, Georgia.

出版信息

J Am Assoc Lab Anim Sci. 2024 May 1;63(3):268-278. doi: 10.30802/AALAS-JAALAS-23-000010. Epub 2024 Feb 29.

DOI:10.30802/AALAS-JAALAS-23-000010
PMID:38423529
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11193426/
Abstract

Nonhuman primates used in biomedical research may experience clinically significant weight loss for a variety of reasons. Episodes of anorexia (complete loss of appetite) or hyporexia (decreased appetite) can result in significant weight loss, potentially altering animal welfare and scientific studies. The FDA has approved several appetite stimulants for use in domestic species, but currently none are approved for use in NHP. Treatment of inappetence and weight loss in NHP often relies on the extralabel use of these compounds. Capromorelin is a ghrelin receptor agonist. As a growth hormone secretagogue, capromorelin increases appetite, leading to weight gain. Studies in several species have shown a positive correlation between capromorelin administration and weight gain; in 2017, an oral solution of capromorelin received FDA approval for use in dogs. We tested this solution in healthy adult rhesus macaques (n = 3 males and 3 females) for its effects on body weight and insulin like growth factor-1 (IGF-1). A control group (n = 2 males and 2 females) was used for comparison. Treated macaques received a 3mg/kg oral dose daily for 7 d. Clinical signs were observed daily. Weights were collected before, during and at the end of treatment. Blood was drawn before, during and after treatment for measurement of IGF-1 levels and standard hematology and biochemistry parameters. Baseline-adjusted mean body weights and IGF-1 levels were significantly higher in treated as compared with control monkeys after 7 d of beginning treatment (body weight of 10.5±0.1kg (mean ± SEM) and 10.1±0.1kg, respectively; IGF-1 of 758±43ng/mL and 639±22ng/mL, respectively). Capromorelin administration was not associated with appreciable changes in hematologic and biochemical values in treated macaques. These findings suggest that capromorelin may be useful for treating inappetence and weight loss in NHP, and based on blood analysis, a 7-d course of treatment does not appear to cause acute toxicity.

摘要

用于生物医学研究的非人类灵长类动物可能会因各种原因出现临床显著的体重减轻。厌食症(完全失去食欲)或食欲减退(食欲减退)发作会导致体重明显减轻,从而改变动物福利和科学研究。FDA 已批准几种食欲刺激剂用于国内物种,但目前尚无一种批准用于 NHP。NHP 中食欲不振和体重减轻的治疗通常依赖于这些化合物的标签外使用。卡普莫瑞林是一种胃饥饿素受体激动剂。作为生长激素促分泌素,卡普莫瑞林增加食欲,导致体重增加。几项研究表明,卡普莫瑞林给药与体重增加之间存在正相关;2017 年,卡普莫瑞林口服溶液获得 FDA 批准用于犬类。我们在健康成年恒河猴(n = 3 只雄性和 3 只雌性)中测试了这种溶液对体重和胰岛素样生长因子-1(IGF-1)的影响。对照组(n = 2 只雄性和 2 只雌性)用于比较。治疗组猴子每天口服 3mg/kg,连续 7 天。每天观察临床症状。在治疗前、治疗中和治疗结束时收集体重。在治疗前、治疗中和治疗后采血,用于测量 IGF-1 水平以及标准血液学和生物化学参数。与对照组相比,开始治疗后 7 天,治疗组猴子的平均基础调整体重和 IGF-1 水平显著升高(体重分别为 10.5±0.1kg(平均值 ± SEM)和 10.1±0.1kg;IGF-1 分别为 758±43ng/mL 和 639±22ng/mL)。卡普莫瑞林给药与治疗组猴子血液学和生化学值的明显变化无关。这些发现表明,卡普莫瑞林可能有助于治疗 NHP 的食欲不振和体重减轻,并且根据血液分析,7 天疗程似乎不会引起急性毒性。

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引用本文的文献

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