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研究小型猪的胃排空率:食物类型和甲氧氯普胺预给药的影响。

Exploring gastric emptying rate in minipigs: Effect of food type and pre-dosing of metoclopramide.

机构信息

School of Pharmacy, University College Cork, Ireland.

Department of Pharmacy, University of Copenhagen, DK-2100 Copenhagen, Denmark.

出版信息

Eur J Pharm Sci. 2018 Jun 15;118:183-190. doi: 10.1016/j.ejps.2018.03.017. Epub 2018 Mar 17.

Abstract

The present study investigated the gastric emptying rate in Göttingen minipigs pre- and post-prandial and evaluated the effect of metoclopramide on the same parameter, using paracetamol as an absorption marker. The pharmacokinetic evaluation of the obtained plasma concentration data for paracetamol demonstrated that the fastest gastric emptying rate was observed in the animals that were allowed access to normal pig food. There was no significant difference in the stomach emptying rate observed between fasted and fed minipigs, when fed either with a FDA standard breakfast or a nutritional energy drink. Pre-dosing minipigs with metoclopramide (0.2 or 0.4 mg/kg) did not demonstrate any effect on gastric emptying in either the fasted or fed state. The data in the present study demonstrated a relatively prolonged gastric emptying rate in mini-pigs both in the fasted and fed state, hence when conducting pharmacokinetic studies using minipigs, this should be taken into account when planning the plasma sampling time points. Further, as no difference could be observed in gastric emptying rate as a function of food, the data also suggest that the Göttingen mini-pigs seems less suited to predict for food effect studies than other species.

摘要

本研究调查了空腹和进食前后哥廷根小型猪的胃排空率,并使用对乙酰氨基酚作为吸收标志物评估了甲氧氯普胺对同一参数的影响。对获得的对乙酰氨基酚血浆浓度数据进行药代动力学评估表明,允许正常食用猪食的动物胃排空速度最快。给予 FDA 标准早餐或营养能量饮料时,空腹和进食小型猪的胃排空率无显著差异。预先给予小型猪甲氧氯普胺(0.2 或 0.4mg/kg),无论空腹还是进食,均未显示对胃排空有任何影响。本研究的数据表明,小型猪在空腹和进食状态下胃排空速度相对较长,因此在使用小型猪进行药代动力学研究时,应在计划血浆采样时间点时考虑到这一点。此外,由于未观察到胃排空率随食物而变化,数据还表明,与其他物种相比,哥廷根小型猪似乎不太适合用于预测食物效应研究。

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