ENHANCED DELIVERY OF GANCICLOVIR TO THE BRAIN THROUGH THE USE OF REDOX TARGETING
ENHANCED DELIVERY OF GANCICLOVIR TO THE BRAIN THROUGH THE USE OF REDOX TARGETING
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DOI：
10.1128/aac.38.4.817
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发表时间：
1994-04-01
影响因子：
4.9
通讯作者：
BODOR, N
中科院分区：
文献类型：
--
作者：
BREWSTER, ME;RAGHAVAN, K;BODOR, N
以氧化还原为基础的化学递送系统证明了更昔洛韦向大脑的递送增强。合成了1-甲基-1，4-二氢烟酸酯与羟甲基官能团共价连接的更昔洛韦单酯。考察了更昔洛韦化学释药系统(DHPG-CDS)在水溶液和器官匀浆中的稳定性。更昔洛韦在大鼠体内的分布研究表明，DHPG-CDS在大鼠体内的分布研究表明，虽然更昔洛韦在中枢神经系统中的渗透性差，并被迅速消除，但DHPG-CDS提供了与治疗相关的药物(2.7um)，并在6h内维持了母体的水平。药物浓度曲线下的面积分析表明，化学给药系统提供的更昔洛韦是母体的5倍。大脑中的高水平和血液中的低水平使更昔洛韦通过化学递送系统输送时的脑与血液药物浓度比为2.54%，而在给予母药时这一比例为0.063。这些数据表明DHPG-CDS。可能是治疗巨细胞病毒脑炎的有效辅助手段。
Enhanced delivery of ganciclovir to the brain was demonstrated by a redox-based chemical delivery system. A ganciclovir monoester in which a 1-methyl-1,4-dihydronicotinate was covalently attached to one of the hydroxymethyl functions was prepared. The stability of the ganciclovir chemical delivery system (DHPG-CDS) was evaluated in aqueous buffers and organ homogenates. In vivo distribution studies in the rat indicated that while ganciclovir poorly penetrated into the central nervous system and was rapidly eliminated, DHPG-CDS provided for therapeutically relevant (2.7 muM) and sustained levels of the parent compound through 6 h. An analysis of the area under the concentration curve indicated that the chemical delivery system delivered five times more ganciclovir than that of the parent drug. The high levels in the brain and reduced levels in the blood gave a brain-to-blood drug concentration ratio of 2.54 for ganciclovir when delivered by the chemical delivery system, compared to a ratio of 0.063 when the parent drug was administered. These data suggest that DHPG-CDS. could be a useful adjunct for the treatment of cytomegalovirus encephalitis.