Pharmacokinetics of Intravesical Doxorubicin in Superficial Bladder Cancer Patients

Abstract

The urine and plasma pharmacokinetics of intravesical doxorubicin were studied in 8 patients with a history of superficial bladder cancer. Patients received 6 weekly treatments of 40mg. doxorubicin in 20ml. physiological saline. Doxorubicin was detectable (0.2ng./ml. or more) in plasma from 6 of 8 patients during the initial treatment. The maximal concentrations ranged from 0.5 to 4.5ng./ml. (mean 1.4). Doxorubicin was not detected in plasma from 7 of 8 patients during treatment 2 and not detected in any patient during treatment 4. The doxorubicin concentrations in urine decreased to approximately 50% at 5 minutes after dosing due to dilution by post-catheterization residual urine, and decreased by a further 6-fold by the end of the 2-hour treatment due to urine production. The recovery of doxorubicin at the end of treatment averaged 88.3%, with an additional recovery of 3.7% during the subsequent 4 hours. Urinary pH (range 5.5 to 8.5) did not affect the stability nor the systemic absorption of doxorubicin. In conclusion, we found that for intravesical doxorubicin therapy there was insignificant systemic exposure to doxorubicin, the highest systemic absorption from the bladder occurred shortly after surgery, there was high target site (bladder tissue) specificity, insignificant metabolism and/or degradation of doxorubicin, and dilution of urinary doxorubicin concentrations and, therefore, decreased tumor exposure to the drug due to residual urine and urine production.