Uno T, Kazui T, Suzuki Y, Hashimoto H, Suzuki K, Muhammad B A
The First Department of Surgery, Hamamatsu University School of Medicine, Shizuoka, Japan.
Lipids. 1999 Mar;34(3):249-54. doi: 10.1007/s11745-999-0360-1.
We developed an oleic acid oil-in-water (o/w)-type emulsion of a new tacrolimus formulation that presented an improvement in the delivery of the drug for oral absorption. This investigation was undertaken to assess a sustained release drug delivery system and selective drug transfer into the lymphatic system. The whole blood concentration profiles after oral administration at a dose of 2 mg/kg and bone marrow, spleen, liver, lung, small intestine, kidney, brain, and whole blood distribution after oral administration at a dose of 1 mg/kg of o/w emulsion formulation of tacrolimus (O/W group) were compared with those of commercially available formulation (T group) in the rat. The mean diameter of the o/w emulsion droplets was 0.47 microm immediately after preparation. The tacrolimus entrapping efficiency of o/w emulsion was 71.3+/-5.0% in 12 h and did not change for 2 d. The area under the whole blood concentration-time curve (AUC) in the O/W group was significantly higher (P<0.01) than that in the T group. In contrast, the values of constant elimination rate and total clearance in the O/W group were significantly lower (P<0.01) than those in the T group, with a comparative bioavailability of 115.9%. The tissue concentration of tacrolimus in the O/W group was significantly higher levels in the bone marrow, spleen, liver, lung, and small intestine, and significantly lower in the brain and kidney, relative to the T group. The o/w emulsion of tacrolimus may be an improved dosage form via the enteral route.
我们开发了一种新型他克莫司制剂的油酸水包油（o/w）型乳剂，该乳剂在药物口服吸收递送方面有所改进。本研究旨在评估一种缓释药物递送系统以及药物向淋巴系统的选择性转移。将他克莫司o/w乳剂制剂（O/W组）以2 mg/kg剂量口服给药后的全血浓度曲线，以及以1 mg/kg剂量口服给药后的骨髓、脾脏、肝脏、肺、小肠、肾脏、脑和全血分布，与大鼠体内市售制剂（T组）进行比较。制备后o/w乳剂液滴的平均直径立即为0.47微米。o/w乳剂的他克莫司包封率在12小时内为71.3±5.0%，并在2天内保持不变。O/W组的全血浓度-时间曲线下面积（AUC）显著高于（P<0.01）T组。相比之下，O/W组的恒速消除率和总清除率值显著低于（P<0.01）T组，相对生物利用度为115.9%。相对于T组，O/W组他克莫司在骨髓、脾脏、肝脏、肺和小肠中的组织浓度显著更高，而在脑和肾脏中显著更低。他克莫司的o/w乳剂可能是一种经肠道给药的改良剂型。
