IMPROVED DELIVERY THROUGH BIOLOGICAL-MEMBRANES - THE EFFECT OF DIHYDRONICOTINATE N-SUBSTITUTION ON THE BRAIN-TARGETING EFFICACY OF A ZIDOVUDINE CHEMICAL DELIVERY SYSTEM

被引：15

作者：

BREWSTER, ME ^{[1
]}

POP, E ^{[1
]}

BRAUNSTEIN, AJ ^{[1
]}

POP, AC ^{[1
]}

DRUZGALA, P ^{[1
]}

DINCULESCU, A ^{[1
]}

ANDERSON, W ^{[1
]}

ELKOUSSI, A ^{[1
]}

BODOR, N ^{[1
]}

机构：

[1] PHARMOS CORP, ALACHUA, FL 32615 USA

来源：

PHARMACEUTICAL RESEARCH | 1993年 / 10卷 / 09期

关键词：

AZIDOTHYMIDINE (ZIDOVUDINE); CHEMICAL DELIVERY SYSTEM; BRAIN; BLOOD BRAIN BARRIER; DIHYDRONICOTINATES; ORGAN TARGETING;

D O I：

10.1023/A:1018986217181

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Enhanced brain delivery of zidovudine (AZT) has been demonstrated using a redox-based chemical delivery system (CDS). Optimization of the prototype AZT-CDS (5'-[(1-methyl-1,4-dihydro-pyridin-3-yl)carbonyl]-3'-azido-3'-deoxythymidine) was investigated by manipulation of the N-methyl group present on the dihydronicotinate portion of the molecule and examining the release of AZT in vivo in a rat model. Of the five compounds examined, all produced higher brain levels and lower blood levels of AZT than did AZT itself. In comparing the novel AZT-CDS analogues to the N-methyl benchmark, the N-propyl system proved to be the most efficient of the compounds tested.

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收藏

页码：1356 / 1362

页数：7

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