Prediction of oral absorption of griseofulvin, a BCS class II drug, based on GITA model:: Utilization of a more suitable medium for in-vitro dissolution study
Prediction of oral absorption of griseofulvin, a BCS class II drug, based on GITA model:: Utilization of a more suitable medium for in-vitro dissolution study
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DOI：
10.1016/j.jconrel.2007.03.002
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发表时间：
2007-06-01
影响因子：
10.8
通讯作者：
Kimura, Toshikiro
中科院分区：
文献类型：
--
作者：
Fujioka, Yoshitsugu;Kadono, Keltaro;Kimura, Toshikiro
由于吸收和/或溶出动力学的较大变异性以及缺乏足够的体外系统来评估药物的体内吸收性，归类为生物药剂学分类系统（BCS）II类的药物的体内吸收性非常难以预测。溶解行为。我们试图预测灰黄霉素，归类为BCS II级，口服粉末给药到大鼠体内的吸收动力学，基于胃肠道转运吸收模型（GITA模型），包括吸收，溶解和GI-运输过程。以JP Ⅰ st溶液、JP Ⅱ nd溶液、FaSSIF、FeSSIF和改良的SIBLM为介质，计算灰黄霉素的溶出速率常数（k（dis）），拟合曲线完全不能描述所观察到的平均血浆曲线。另一方面，通过采用利用MREVID 2获得的k（dis）提供的计算线（反映体内溶出度的介质2），一种新的介质，与现有介质相比，这表明，利用适当的k（dis）值可以预测输入。基于GITA模型归类为BCS II类药物的体内吸收动力学，MREVID 2可能是描述体内溶出动力学的有用介质。(C)2007 Elsevier B. V.保留所有权利。
The in-vivo absorbability of drugs categorized into the biopharmaceutics classification system (BCS) class II is very difficult to be predicted because of the large variability in the absorption and/or dissolution kinetics and the lack of an adequate in-vitro system for evaluating the dissolution behavior. We tried to predict the in-vivo absorption kinetics of griseofulvin, categorized into BCS class II, orally administrated as powders into rats, based on Gastrointestinal-Transit-Absorption model (GITA model), consisting of the absorption, dissolution and GI-transit processes. Using the dissolution rate constants (k(dis)) of griseofulvin obtained with JP I st solution, JP 2nd solution, FaSSIF, FeSSIF and modified SIBLM as a medium, simulation lines were not able to describe the observed mean plasma profile at all. On the other hand, a calculated line provided by employing k(dis) obtained with MREVID 2 (medium reflecting in-vivo dissolution 2), a new medium, was in better agreement with the observed mean plasma profile than existing media, indicating that the utilization of adequate k(dis) value made it possible to predict the in-vivo absorption kinetics of drugs classified into BCS class II based on GITA model and that MREVID 2 could be a useful medium for describing the in-vivo dissolution kinetics. (C) 2007 Elsevier B.V. All rights reserved.