The effect of fasting or desmopressin before treatment on the concentration of mitomycin C during intravesical administration.

Abstract

To evaluate two methods of reducing the urine output during treatment (the most easily manipulated variable) in patients undergoing intravesical instillation with mitomycin C, where the concentration-time curve also depends upon dose, diluent volume, residual urine volume, and drug absorption and degradation. The study comprised 20 consecutive patients undergoing a course of six weekly instillations of mitomycin C (40 mg in 40 mL for 1 h) for superficial bladder carcinoma. Urine production during treatment was calculated by adding the voided volume and ultrasonographically measured residual urine after treatment, and subtracting 40 mL; the patient's bladder was emptied before instillation. Before the first and second visit the patients were asked to drink normally. Before the third and fourth visit patients fasted for 6 h before treatment. For the fifth and sixth visit the patients had not fasted, but 200 microg of desmopressin was given orally 1 h before instillation. Any urinary side-effects were graded on a four-point scale. There were 17 patients with complete data; one patient failed to take desmopressin, one had detrusor instability and one developed chemical cystitis. The mean (SD) urine production in unprepared patients was 209 (123) mL, which decreased to 143 (80) mL (P = 0.039, t-test) after fasting and 103 (51) mL (P < 0.001) with desmopressin. This equates to a 20% increase in mean intravesical drug concentration with fasting and a 38% increase with desmopressin. Urinary side-effects were graded as mild in each group. Unprepared patients produce variable and often substantial volumes of urine during intravesical chemotherapy. There was a significant reduction in urine output after fasting or by administering desmopressin before instillation. These measures increase the area under the concentration-time curve for mitomycin C and potentially increase the efficacy of treatment.