Advance in the pharmacology of buthionine salfoximine / 中国药理学通报

ABSTRACT

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.