Peterson Larryn W, McKenna Charles E
University of Southern California, Department of Chemistry, Los Angeles, CA 90089-0744, USA.
Expert Opin Drug Deliv. 2009 Apr;6(4):405-20. doi: 10.1517/17425240902824808.
Nucleotide analogues have been well accepted as therapeutic agents active against a number of viruses. However, their use as antiviral agents is limited by the need for phosphorylation by endogenous enzymes, and if the analogue is orally administered, by low bioavailability due to the presence of an ionizable diacid group. To circumvent these limitations, a number of prodrug approaches have been proposed. The ideal prodrug achieves delivery of a parent drug by attachment of a non-toxic moiety that is stable during transport and delivery, but is readily cleaved to release the parent drug once at the target. Here, a brief overview of several promising prodrug strategies currently under development is given.
核苷酸类似物已被广泛认可为对多种病毒具有活性的治疗药物。然而，它们作为抗病毒药物的应用受到内源性酶磷酸化需求的限制，并且如果该类似物是口服给药，则由于存在可电离的二酸基团而生物利用度较低。为了克服这些限制，已经提出了多种前药方法。理想的前药是通过连接一个无毒部分来实现母体药物的递送，该无毒部分在运输和递送过程中是稳定的，但一旦到达靶点就很容易裂解以释放母体药物。在此，简要概述了目前正在开发的几种有前景的前药策略。
