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吲哚美辛胶囊在人体中的生物利用度(III):与比格犬生物利用度的相关性。

Bioavailability of indomethacin capsules in humans (III): Correlation with bioavailability in beagle dogs.

作者信息

Aoyagi N, Ogata H, Kaniwa N, Ejima A, Nakata H, Tsutsumi J, Fujita T, Amada I

出版信息

Int J Clin Pharmacol Ther Toxicol. 1985 Nov;23(11):578-84.

PMID:4077308
Abstract

The bioavailabilities of five indomethacin capsules were studied in ten beagle dogs and correlations with the in vivo results in humans and dissolution rates were investigated. The difference in bioavailability between two commercial products was smaller in dogs than in humans, which seemed to be due to strong disintegration forces in dogs. The difference in the dissolution rate among the products was reflected less in the Tmax in dogs than in humans, and the Tmax was shorter in dogs which seems to be due to faster gastric emptying and passage of the drug through the absorption site in dogs. Gastric acidity effects on the indomethacin availability found in humans were not observed in dogs. The Cmax and Tmax correlated well with the in vitro dissolution rates, but AUC24 did not. The Cmax and Tmax in dogs also correlated with the corresponding parameters in humans, especially those in high gastric acidity humans, but AUC24 did not.

摘要

在十只比格犬中研究了五种吲哚美辛胶囊的生物利用度,并研究了其与人体体内结果及溶出速率的相关性。两种市售产品之间的生物利用度差异在犬中比在人体中更小,这似乎是由于犬体内较强的崩解力所致。产品之间溶出速率的差异在犬的达峰时间(Tmax)中体现得比在人体中少,且犬的Tmax更短,这似乎是由于犬的胃排空更快以及药物通过吸收部位的速度更快。在犬中未观察到人体中发现的胃酸度对吲哚美辛生物利用度的影响。峰浓度(Cmax)和达峰时间与体外溶出速率相关性良好,但24小时药时曲线下面积(AUC24)并非如此。犬的Cmax和Tmax也与人体中的相应参数相关,尤其是高胃酸度人群中的参数,但AUC24并非如此。

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