Species Differences in the Metabolism and Disposition of Antiviral Nucleoside Analogues: 1. Acyclovir
Species Differences in the Metabolism and Disposition of Antiviral Nucleoside Analogues: 1. Acyclovir
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DOI：
10.1177/095632029200300101
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发表时间：
1992-02
影响因子：
--
通讯作者：
P. D. de Miranda;S. Good
中科院分区：
文献类型：
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作者：
P. D. de Miranda;S. Good
无环核苷类似物阿昔洛韦是一种抗病毒药物，具有对抗疱疹 DNA 病毒的活性。临床上用作治疗单纯疱疹和水痘带状疱疹病毒感染的选择性治疗剂。在阿昔洛韦的临床前和临床开发过程中对其处置的研究表明，该药物的吸收、代谢和消除存在显着的物种差异。狗和小鼠的胃肠道吸收充足；但在大鼠和灵长类动物中，剂量限制在低于给药剂量的 20%。尽管在某些物种（小鼠、大鼠和狗）中，阿昔洛韦实际上未代谢，但在豚鼠、兔子和一些灵长类动物中，明显发生了显着的生物转化。阿昔洛韦组织分布广泛，不同物种之间差异不大。本综述总结了关于阿昔洛韦在包括人类在内的不同物种中吸收、代谢和处置的各种研究，并指出了此类研究在药物开发中的相关性和重要性。
The acyclic nucleoside analogue, acyclovir, is an antiviral drug with activity against the herpes group of DNA viruses. Clinically, it is used as a selective therapeutic agent for the treatment of herpes simplex and varicella-zoster virus infections. Studies on the disposition of acyclovir, during the course of its preclinical and clinical development, indicated significant species differences in the absorption, metabolism and elimination of the drug. Gastrointestinal absorption was adequate in dogs and in mice; but in rats and primates it was limited to less than 20% of the administered dose. Whereas in some species (mice, rats, and dogs), acyclovir was virtually unmetabolized, significant biotransformation was apparent in guinea pigs, rabbits, and some primates. Acyclovir tissue distribution was extensive and indicated few differences across species. This review summarizes diverse studies on acyclovir absorption, metabolism, and disposition in different species, including humans, and indicates the relevance and importance of such studies in drug development.