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兽医物种胃肠道差异对兽用治疗药物口服溶解度、体内溶出及制剂的影响。

Impact of gastrointestinal differences in veterinary species on the oral drug solubility, in vivo dissolution, and formulation of veterinary therapeutics.

作者信息

Martinez Marilyn N, Papich Mark G, Fahmy Raafat

机构信息

Office of New Animal Drug Evaluation, Center for Veterinary Medicine, US Food and Drug Administration, Rockville, Maryland,

College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina,

出版信息

ADMET DMPK. 2022 Feb 14;10(1):1-25. doi: 10.5599/admet.1140. eCollection 2022.

Abstract

Many gaps exist in our understanding of species differences in gastrointestinal (GI) fluid composition and the associated impact of food intake and dietary composition on in vivo drug solubilization. This information gap can lead to uncertainties with regard to how best to formulate pharmaceuticals for veterinary use or the in vitro test conditions that will be most predictive of species-specific in vivo oral product performance. To address these challenges, this overview explores species-specific factors that can influence oral drug solubility and the formulation approaches that can be employed to overcome solubility-associated bioavailability difficulties. These discussions are framed around some of the basic principles associated with drug solubilization, reported species differences in GI fluid composition, types of oral dosage forms typically given for the various animal species, and the effect of prandial state in dogs and cats. This basic information is integrated into a question-and-answer section that addresses some of the formulation issues that can arise in the development of veterinary medicinals.

摘要

我们对胃肠道(GI)液成分的物种差异以及食物摄入和饮食组成对体内药物溶解的相关影响了解尚存在许多空白。这种信息差距可能导致在如何为兽医用途优化药物制剂或哪种体外测试条件最能预测特定物种的体内口服产品性能方面存在不确定性。为应对这些挑战,本综述探讨了可能影响口服药物溶解度的物种特异性因素以及可用于克服与溶解度相关的生物利用度难题的制剂方法。这些讨论围绕与药物溶解相关的一些基本原则、已报道的胃肠道液成分的物种差异、通常给予各种动物物种的口服剂型类型以及犬猫进食状态的影响展开。这些基本信息被整合到一个问答环节中,该环节解决了兽药开发中可能出现的一些制剂问题。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce8c/8963575/66493b722900/Admet-10-1140-g001.jpg

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