The Effect of Entrapment in Liposomes on the in Vivo Distribution of [3H]Methotrexate in a Primate

摘要: Summary Entrapment of methotrexate (MTX) plus [3′,5′, 9(n)-3H]methotrexate into positively charged liposomes greatly alters the subsequent distribution [3H]MTX in a cynomolgous monkey (Macaca irus) after single i.v. injection ([3H]MTX; refers to total radioactivity derived from purified [3H]MTX). When is incorporated small, sonically disrupted liposomes, level entrapped plasma volume was still 50% injected dose 4 hr, which 100 times greater than found when same amount free MTX (1 mg) injected. larger mechanically dispersed however, levels liposome-entrapped at hr only 6-fold [3H]MTX. The (refers measured by dihydrofolate reductase assay) did not show detectable breakdown whereas showed up 97% breakdown. Increased clearance complemented its much uptake tissues, especially spleen, compared with liposomes. There over 160-fold increased spleen relative [3H]MTX, for comparable ratio 20. Although this significant breakdown, it less that MTX. In certain small intestine, reduced found. Uptake led lower renal case Possible reasons these effects and relationship our findings those others are discussed.