Amelioration of Cyclophosphamide-Induced Cystitis

Summary

The use of acetylcysteine (Mucomyst) to prevent cyclophosphamide-induced cystitis was studied. The acetylcysteine was given to 6 purebred beagle dogs and 6 rhesus monkeys by bladder irrigation with a 2-catheter technique. No toxicity was associated with this procedure. After cyclophosphamide treatment (30 mg/kg intravenously as a single dose), no 4(-p-nitrobenzyl)pyridine reactivity (alkylating ability) was found in the urine after acetylcysteine bladder irrigation. These animals also had significantly less cystitis. Urine containing the active metabolite was obtained from dogs given cyclophosphamide (125 mg/kg intravenously). It was added to acetylcysteine or normal saline in a ratio of 1 to 2, and these solutions were instilled into the bladders of normal dogs. These animals were killed after 24 hours. The dogs receiving urine with the activated product plus saline had significant cystitis, whereas those receiving urine with activated product and acetylcysteine had only minimal histologic changes. Thus bladder irrigation with acetylcysteine during cyclophosphamide therapy might be a valuable therapeutic adjuvant.