STUDIES OF PHARMACOKINETICS AND THERAPEUTIC EFFECTS OF GLUCOCORTICOIDS ENTRAPPED IN LIPOSOMES AFTER INTRAARTICULAR APPLICATION IN HEALTHY RABBITS AND IN RABBITS WITH ANTIGEN-INDUCED ARTHRITIS
STUDIES OF PHARMACOKINETICS AND THERAPEUTIC EFFECTS OF GLUCOCORTICOIDS ENTRAPPED IN LIPOSOMES AFTER INTRAARTICULAR APPLICATION IN HEALTHY RABBITS AND IN RABBITS WITH ANTIGEN-INDUCED ARTHRITIS
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DOI：
10.1007/bf00541378
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发表时间：
1987-01-01
影响因子：
4
通讯作者：
WEDER, HG
中科院分区：
文献类型：
--
作者：
BONANOMI, MH;VELVART, M;WEDER, HG
将地塞米松棕榈酸酯（DMP）包裹在一定大小的脂质体中，在健康家兔和抗原诱导关节炎家兔关节内注射。采用微晶曲安奈德（TAC）测定脂质体DMP的药代动力学和治疗效果，并与相应实验进行比较。小DMP脂质体（直径160 nm）比30倍剂量的微晶TAC显示更大的关节周长减少。此外，约98%的给药TAC在注射后6 h已从关节中消失，而约36%的脂质体DMP仍在滑液和滑膜中同时检测到。将囊泡直径从160 nm增加到750 nm（大脂质体），在健康家兔注射后48 h内，DMP的保留率提高了2.6倍。此外，没有一种脂质体糖皮质激素制剂能够抑制内源性血浆皮质醇水平，这与微晶制剂的抑制作用形成对比。
Dexamethasone palmitate (DMP) entrapped in liposomes of defined sizes was administered intraarticularly in healthy rabbits and in rabbits with antigen-induced arthritis. The pharmacokinetics and therapeutic effect of liposomal DMP were measured and compared with corresponding experiments using microcrystalline triamcinolone acetonide (TAC). The small DMP liposomes (diameter 160 nm) showed a greater decrease in joint circumference than the 30 times-higher dose of microcrystalline TAC. Moreover, about 98% of administered TAC had already disappeared from the joint 6 h after injection, whereas about 36% of liposomal DMP was still measured in synovial fluid and synovium at the same time. Increasing the vesicle diameter from 160 to 750 nm (large liposomes) improved the retention of DMP by a factor of 2.6 within 48 h after injection in healthy rabbits. In addition, none of the liposomal glucocorticoid preparations ever suppressed the endogenous plasma cortisol level, which is in contrast to the suppression measured after administration of the microcrystalline preparation.