Prediction Accuracy of Mechanism-Based Oral Absorption Model for Dogs
| Autor: | Miyake Shuji, Takahiro Kimoto, Toshio Taniguchi, Soichiro Ito, Kiyohiko Sugano, Yoshiyuki Akiyama, Hanae Mukumoto, Takuya Fujita, Yukihiro Nomura, Naoya Matsumura |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Chromatography Chemistry Free acid Administration Oral Pharmaceutical Science Mechanism based 02 engineering and technology Absorption (skin) Hydrogen-Ion Concentration 021001 nanoscience & nanotechnology Appropriate use Models Biological 030226 pharmacology & pharmacy 03 medical and health sciences Dogs 0302 clinical medicine Intestinal Absorption Pharmaceutical Preparations Solubility Animals Female 0210 nano-technology Literature survey |
| Zdroj: | Journal of Pharmaceutical Sciences. 108:2728-2736 |
| ISSN: | 0022-3549 |
| DOI: | 10.1016/j.xphs.2019.03.015 |
| Popis: | The purpose of the present study was to evaluate the prediction accuracy of a mechanism-based oral absorption model for the fraction of a dose absorbed (Fa) in dogs, focusing on poorly soluble drugs. As an open mechanism-based model, the gastrointestinal unified theoretical framework was used in this study. The prediction accuracy of the gastrointestinal unified theoretical framework was evaluated using Fa data in dogs (63 data sets for marketed drugs and proprietary compounds). For neutral compounds, Fa was accurately predicted, suggesting that the physiological parameters of dogs were appropriate except for gastrointestinal pH. An extensive literature survey on the small intestinal pH of dogs was then conducted. The result suggested that the pH value ranged between 6.5 and 7.5, with the midst value of 7.0, but there was a great variation among the literature. To confirm the appropriateness of this pH value, the Fa of free acid compounds was predicted by setting the small intestinal pH to 6.5, 7.0, and 7.5. The proportions of compounds with |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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