丁硫氨酸亚砜胺的药理学研究进展

Advance in the pharmacology of buthionine salfoximine

丁硫氨酸亚砜胺（BSO）是一个正处于临床研究的肿瘤化疗增敏剂。体内外研究表明BSO可逆转肿瘤细胞的多药耐药性。本文对其作用机制、药效学、药代动力学及临床研究作综述。BSO是谷胱甘肽合成过程中的限速酶γ-谷氨酰胺半胱氨酸合成酶的抑制剂。体外细胞培养实验表明以BSO降低组织细胞内谷胱甘肽的水平,可逆转多种对顺铂及烷化剂等化疗药物耐药的肿瘤细胞的耐药性。体内实验中BSO可提高化疗药物的治疗指数,延长荷瘤动物的寿命。BSO动力学在小鼠、犬和人均呈二室模型。BS0目前处于临床研究,对癌症病人的化疗增敏效果正在考察。

Buthionine salfoximine (BSO) is a chemotherapeutic sensitizor under clinical trial. BSO can reverse multidrug resistance in vitro and in vivo. The author reviewed the mechanism, pharmacodynamics, pharmacokinetics and the progress in clinical research of BSO. BSO is a selective inhibitor of 7-glutamylcysteine synthetase, the rate-limiting enzyme in gluthionine synthesis. Depletion of intracellular gluthionine by BSO can reverse tumor resistance to chemotherapeutic a-gents such as platinating and alkylating agents. In tumor-bearing animals BSO enhanced the therapeutic index of chemotherapeutic agents. Animals treated with BSO had a longer life span. Pharmacokinetics of BSO was a two-compartment manner in mice, dogs and huamn beings. The efficacy of BSO in cancer patients is being investigated in clinical trial.