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Pharmacokinetics And Therapeutic Uses Of Mesna, Murray J. Cutler

Electronic Thesis and Dissertation Repository

In the early 1980s, significant advancement in the safety of ifosfamide therapy was achieved by co-administrating mesna (sodium 2-mercaptoethane sulfonate) to prevent dose-limiting hemorrhagic cystitis. Mesna exerts its protective effect within the urine, where its free sulfhydryl group is able to conjugate cytotoxic metabolites. Within the circulation, however, mesna exists primarily as its inactive disulfide, dimesna. Dimesna is currently undergoing clinical development as a prodrug (BNP7787) to treat cisplatin-induced nephrotoxicity. Remarkably, chemoprotection is achieved without attenuation of efficacy of co-administered anti-cancer agents. This is widely attributed to the kidney-specific disposition and stability of dimesna.

We sought to evaluate the role …