喜树碱类抗肿瘤药内酯型/羧酸盐型平衡研究进展

Current status of lactone/carboxylate salt equilibria of camptothecin as antitumor agents

喜树碱类药物是抗肿瘤药物领域的研究热点之一。喜树碱类药物以内酯型和羧酸盐型2种形式存在,其中内酯型为公认的主要有效形式。文中分别阐述了pH、血液成分、药动学、制剂等多因素对喜树碱类药物内酯型/羧酸盐型的平衡影响,通过制剂手段可以提高具有生物活性的喜树碱类药物内酯型在体内的稳定性,延长药物在血浆中的滞留时间,提高抗癌活性,提示若能提高这类药物内酯型在体内靶部位浓度比,则能增强这类药物抗肿瘤的疗效。

The camptothecins （CPTs） are one of the hot spots in the study of antitumor drugs. There are two forms： lactone and carboxylate, and lactone is the valid form. The effect of pH, blood and preparation on lactone/carboxylate salt equilibria of camptothecins, and the pharmacokinetics of lactone/carboxylate salt were reviewed. The preparation can improve the stability of lactone in vivo, extend the plasma residence time of the drug, and improve the antitumor activity. These suggest that increasing the stability of active lactone in vivo can enhance the antitumor activity.