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鉴定比格犬的摄食模式和用于评估生物利用度的食物效应方案。

来源:萌宠菠菠乐园 时间:2025-10-20 16:43

Abstract

Food is a known primary role to the exposure of the drugs orally administered. Since each animal may have unique food taking pattern and it is difficult to manipulate the food taking to animals, there lacks rationalized protocol for the food effects in pre-clinic study. The objective of this study was to identify the beagle food taking patterns and demonstrate their effects on bioavailability in valsartan. Herein, four types of food taking patterns of beagle were identified via inter-day and intra-day analysis, and named as Persisting, Pulsing, Postponing, Pushing ("4P Modes"), respectively, which were also validated by principal component analysis (PCA). Interestingly, food intake resulted in a reduced area under the concentration-time curve (AUC), maximum concentration (C) and absorption rate, whilst the reduction varied in "4P Modes" of food taking. General considerations in the design of experiment for food effect to the bioavailability in beagles have been established as: to recognize the food taking patterns in each animal, to confirm the inter-day stability of the food taking behaviors, to trace the food taking patterns in parallel with plasma sampling. In conclusion, the right animals with proper food taking patterns should be assessed and selected for pre-clinic bioavailability evaluations.

摘要

食物是口服给予药物暴露的已知主要途径。由于每只动物可能具有独特的进食模式,并且难以操纵动物的进食行为,因此在临床前研究中缺乏针对食物影响的合理化方案。本研究的目的是确定比格犬的进食模式,并证明其对缬沙坦生物利用度的影响。在此,通过日间和日内分析确定了比格犬的四种进食模式,分别命名为持续进食模式(Persisting)、脉冲进食模式(Pulsing)、延迟进食模式(Postponing)和推进进食模式(Pushing)(简称“4P 模式”),并通过主成分分析(PCA)进行了验证。有趣的是,食物摄入导致浓度-时间曲线下面积(AUC)、最大浓度(C)和吸收速率降低,而降低的幅度在不同的“4P 模式”之间存在差异。在设计用于评估比格犬生物利用度的食物影响实验时,需要考虑以下因素:识别每个动物的进食模式,确认进食行为的日间稳定性,以及在进行血浆采样的同时跟踪进食模式。总之,应评估和选择具有适当进食模式的合适动物进行临床前生物利用度评估。

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