Prevention of urotoxic side effects by regional detoxification with increased selectivity of oxazaphosphorine cytostatics.
Paraules clau
Resum
Urotoxic side effects, particularly haemorrhagic cystitis, have been a limiting factor for the therapeutic use of the oxazaphosphorine cytostatics cyclophosphamide, ifosfamide and trofosfamide. The development of mesna (Uromitexan) has made it possible to carry out regional detoxification in the kidneys and the efferent urinary tract and thus to achieve clinically prophylaxis against the urotoxic side effects of oxazaphosphorines. In the body, mesna is rapidly converted to the biologically inactive disulfide form (dimesna). After glomerular filtration, dimesna is reduced by interaction with the glutathione system of the renal tubular cells and is excreted in the urine as mesna, the free thiol compound. This compound is then capable of definitively detoxifying the oxazaphosphorine metabolites in the urine. In extensive experiments on rats, it has been demonstrated that the cyclophosphamide-induced occurrence of urinary bladder tumours could be reduced or even eliminated by simultaneous administration of mesna. Detoxification by mesna enables the clinical use of higher doses and, consequently, a possible increase in therapeutic efficiency.