Effects and systemic uptake of the new mitomycin C analogue KW-2149 in beagle dogs after intravesical administration.

The present study was designed to evaluate the local effects of the new mitomycin C analogue KW-2149 after intravesical instillation, together with its penetration into the systemic circulation in healthy beagle dogs. Two reference dogs were treated with two instillations of mitomycin C (30 mg in 30 ml phosphate buffer). Four dogs were given two, three, four and six instillations, respectively, of KW-2149 (60 mg in 30 ml phosphate buffer). KW-2149 concentrations measured in the systemic circulation were very low and were frequently found to be below the limit of determination. The number of instillations had no influence on the KW-2149 concentrations measured in the systemic circulation. Blood analysis showed no systemic toxicity. The histopathological findings in the bladder were comparable in both groups. The number of instillations had no influence on the severity of the lesions found in the bladder wall. On the basis of its in vitro activity KW-2149 can be regarded as a promising agent for intravesical treatment of superficial bladder cancer.