Brain-targeted prodrugs of azidothymidine

Toshikiro Kimura; Masahide Onogawa; Eri Yanamoto; Yuji Kurosaki; Taiji Nakayama; Noriko Mizobuchi; Ryoji Konishi; Kouki Kitagawa

doi:10.2745/dds.10.413

Brain-targeted prodrugs of azidothymidine

Toshikiro Kimura, Masahide Onogawa, Eri Yanamoto, Yuji Kurosaki, Taiji Nakayama, Noriko Mizobuchi, Ryoji Konishi, Kouki Kitagawa

Research output: Contribution to journal › Article › peer-review

Abstract

Five azidothymidine (AZT) prodrugs conjugated with the 1-adamantane moiety or the acyl group via an ester bond were evaluated as the brain-directed prodrug in rats. All the prodrugs showed the high lipophilicity and four of them were rapidly degraded to AZT in both plasma and brain homogenates. Adamantanecarbonyl-AZT (Ada-AZT2) was stable in both plasma and brain homogenates. After intravenous bolus administration of the prodrugs, improved brain AZT levels were observed only in acetyl-AZT (C₂-AZT) and decanoyl-AZT (C₁₀-AZT). Ada-AZT2 was highly delivered to the brain in the early time point but was rapidly cleared and the generation of AZT was not observed in the brain. The favorable nature for brain-targeted prodrugs was discussed.

Original language	English
Pages (from-to)	413-417
Number of pages	5
Journal	Drug Delivery System
Volume	10
Issue number	6
DOIs	https://doi.org/10.2745/dds.10.413
Publication status	Published - 1995

Keywords

AZT
azidothymidine
brain-targeting
prodrug

ASJC Scopus subject areas

Pharmaceutical Science

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10.2745/dds.10.413

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abstract = "Five azidothymidine (AZT) prodrugs conjugated with the 1-adamantane moiety or the acyl group via an ester bond were evaluated as the brain-directed prodrug in rats. All the prodrugs showed the high lipophilicity and four of them were rapidly degraded to AZT in both plasma and brain homogenates. Adamantanecarbonyl-AZT (Ada-AZT2) was stable in both plasma and brain homogenates. After intravenous bolus administration of the prodrugs, improved brain AZT levels were observed only in acetyl-AZT (C2-AZT) and decanoyl-AZT (C10-AZT). Ada-AZT2 was highly delivered to the brain in the early time point but was rapidly cleared and the generation of AZT was not observed in the brain. The favorable nature for brain-targeted prodrugs was discussed.",

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AU - Kimura, Toshikiro

AU - Onogawa, Masahide

AU - Yanamoto, Eri

AU - Kurosaki, Yuji

AU - Nakayama, Taiji

AU - Mizobuchi, Noriko

AU - Konishi, Ryoji

AU - Kitagawa, Kouki

PY - 1995

Y1 - 1995

N2 - Five azidothymidine (AZT) prodrugs conjugated with the 1-adamantane moiety or the acyl group via an ester bond were evaluated as the brain-directed prodrug in rats. All the prodrugs showed the high lipophilicity and four of them were rapidly degraded to AZT in both plasma and brain homogenates. Adamantanecarbonyl-AZT (Ada-AZT2) was stable in both plasma and brain homogenates. After intravenous bolus administration of the prodrugs, improved brain AZT levels were observed only in acetyl-AZT (C2-AZT) and decanoyl-AZT (C10-AZT). Ada-AZT2 was highly delivered to the brain in the early time point but was rapidly cleared and the generation of AZT was not observed in the brain. The favorable nature for brain-targeted prodrugs was discussed.

AB - Five azidothymidine (AZT) prodrugs conjugated with the 1-adamantane moiety or the acyl group via an ester bond were evaluated as the brain-directed prodrug in rats. All the prodrugs showed the high lipophilicity and four of them were rapidly degraded to AZT in both plasma and brain homogenates. Adamantanecarbonyl-AZT (Ada-AZT2) was stable in both plasma and brain homogenates. After intravenous bolus administration of the prodrugs, improved brain AZT levels were observed only in acetyl-AZT (C2-AZT) and decanoyl-AZT (C10-AZT). Ada-AZT2 was highly delivered to the brain in the early time point but was rapidly cleared and the generation of AZT was not observed in the brain. The favorable nature for brain-targeted prodrugs was discussed.

KW - AZT

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Brain-targeted prodrugs of azidothymidine

Abstract

Keywords

ASJC Scopus subject areas

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