Venkataram S, Rogers J A
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
J Pharm Sci. 1988 Nov;77(11):933-6. doi: 10.1002/jps.2600771106.
The bioavailabilities of griseofulvin and dimyristoylphosphatidylcholine (DMPC) coprecipitates prepared from chloroform have been determined in rats. The dissolution rate of griseofulvin in pH 2.0 HCl:KCl buffer under sink conditions increased nonlinearly with an increase in DMPC in the coprecipitates. The initial dissolution rate, the amount dissolved after 60 min, Cmax, and AUC were all approximately twofold greater for coprecipitates than for griseofulvin over the range of 19:1 to 1.5:1 griseofulvin:DMPC weight ratio. In contrast, physical mixtures of griseofulvin:DMPC yielded results which were not significantly different from those of griseofulvin alone. The correlation between in vitro and in vivo parameters was at least 0.95. Thus, the reduction in particle size and solubilization of griseofulvin which is observed in vitro are believed to also occur in vivo and provide improved bioavailabilities.
已在大鼠体内测定了由氯仿制备的灰黄霉素与二肉豆蔻酰磷脂酰胆碱（DMPC）共沉淀物的生物利用度。在漏槽条件下，灰黄霉素在pH 2.0的HCl:KCl缓冲液中的溶解速率随着共沉淀物中DMPC含量的增加而非线性增加。在灰黄霉素与DMPC重量比为19:1至1.5:1的范围内，共沉淀物的初始溶解速率、60分钟后溶解的量、Cmax和AUC均比灰黄霉素约高两倍。相比之下，灰黄霉素与DMPC的物理混合物产生的结果与单独使用灰黄霉素的结果没有显著差异。体外和体内参数之间的相关性至少为0.95。因此，体外观察到的灰黄霉素粒径减小和增溶作用据信在体内也会发生，并能提高生物利用度。
