EFFECTS AND SYSTEMIC UPTAKE OF THE NEW MITOMYCIN-C ANALOG KW-2149 IN BEAGLE DOGS AFTER INTRAVESICAL ADMINISTRATION

The present study was designed to evaluate the local effects of the ne w mitomycin C analogue KW-2149 after intravesical instillation, togeth er with its penetration into the systemic circulation in healthy beagl e dogs. Two reference dogs were treated with two instillations of mito mycin C (30 mg in 30 ml phosphate buffer). Four dogs were given two, t hree, four and six instillations, respectively, of KW-2149 (60 mg in 3 0 ml phosphate buffer). KW-2149 concentrations measured in the systemi c circulation were very low and were frequently found to be below the limit of determination. The number of instillations had no influence o n the KW-2149 concentrations measured in the systemic circulation. Blo od analysis showed no systemic toxicity. The histopathological finding s in the bladder were comparable in both groups. The number of instill ations had no influence on the severity of the lesions found in the bl adder wall. On the basis of its in vitro activity KW-2149 can be regar ded as a promising agent for intravesical treatment of superficial bla dder cancer.