| Autor: |
Carlert, Sara, Åkesson, Pernilla, Jerndal, Gunilla, Lindfors, Lennart, Lennernäs, Hans, Abrahamsson, Bertil |
| Zdroj: |
Molecular Pharmaceutics; October 2012, Vol. 9 Issue: 10 p2903-2911, 9p |
| Abstrakt: |
The purpose of this study was to investigate in vivointestinal precipitation of a model drug mebendazole, a basic BCS class II drug, using dogs with intestinal stomas for administration or sampling. After oral administration of a solution with an expected intestinal supersaturation of approximately 20 times the solubility, the measured supersaturation in dog intestinal fluid (DIF) was up to 10 times and, on average, only 11% of the given dose was retrieved as solid drug in the collected fluid from the stoma. The drug was rapidly absorbed with >90% of the total systemic exposure reached within three hours after duodenal administration of a solution. In silicoabsorption modeling showed that in vivodata were reasonably well described by a nonprecipitating solution. An in vitromodel of precipitation in DIF predicted that the intestinal concentration of dissolved mebendazole would be less than 1/5 of the initial concentration within 10 min at concentrations comparable to in vivo. It was concluded that intestinal precipitation did not have any major influence on mebendazole absorption. The extent of precipitation was overpredicted in vitrogiven the in vivoabsorption rate, and further work is needed to identify in vitrofactors that could enable more accurate in vivopredictions of intestinal precipitation from solutions. |
| Databáze: |
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