PHARMACOKINETICS OF LIPOSOME-ENCAPSULATED ANTI-TUMOR DRUGS - STUDIES WITH VINBLASTINE, ACTINOMYCIN-D, CYTOSINE-ARABINOSIDE, AND DAUNOMYCIN
PHARMACOKINETICS OF LIPOSOME-ENCAPSULATED ANTI-TUMOR DRUGS - STUDIES WITH VINBLASTINE, ACTINOMYCIN-D, CYTOSINE-ARABINOSIDE, AND DAUNOMYCIN
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DOI：
10.1016/0006-2952(78)90252-6
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发表时间：
1978-01-01
影响因子：
5.8
通讯作者：
STAMP, D
中科院分区：
文献类型：
--
作者：
JULIANO, RL;STAMP, D
本文研究了脂质体（磷脂囊泡）对长春碱、阿糖胞苷、放线菌素D和柔红霉素等4种抗肿瘤药物在大鼠体内的血浆清除动力学和组织分布的影响。在每种情况下，静脉给药后，脂质体包封的药物从血浆中清除的速度比游离药物慢。以游离形式注射的大部分柔红霉素的血浆半衰期小于5分钟，而脂质体包封的柔红霉素的血浆半衰期超过150分钟。包封也引起了显着的改变，在注射药物的组织处置。脂质体内的包封导致注射后不同时间组织保留的药物当量总量大幅增加。在阿糖胞苷的情况下，注射后16小时肝脏中的药物当量水平是脂质体包封药物的68倍，比游离药物高。包封也改变了药物在组织中的相对分布，富含网状内皮细胞的组织，如肝脏和脾脏，是摄取的有利部位。
The effects of encapsulation within liposomes (phospholipid vesicles) on the plasma clearance kinetics and tissue disposition of 4 antitumor drugs, vinblastine, cytosine arabinoside, actinomycin-D and daunomycin were investigated in rats. In each case, subsequent to i.v. administration the liposome-encapsulated drugs were cleared from the plasma more slowly than the free drugs. The major portion of daunomycin injected in free form had a plasma half-life of less than 5 min, while liposome-encapsulated daunomycin had a plasma half-life in excess of 150 min. Encapsulation also caused a marked alteration in the tissue disposition of the injected drugs. Encapsulation within liposomes resulted in a large increase in the total amount of drug equivalents retained by the tissues at various times after injection. In the case of cytosine arabinoside, the level of drug equivalents in the liver at 16 h postinjection was 68-fold greater for liposome-encapsulated drug than free drug. Encapsulation also altered the relative distribution of drugs in the tissues, with tissues rich in reticuloendothelial cells, such as liver and spleen, being the favored sites of uptake.