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

Abstract

Objective 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. Patients and methods 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 super®cial 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 ®rst 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 ®fth and sixth visit the patients had not fasted, but 200 mg of desmopressin was given orally 1 h before instillation. Any urinary side-effects were graded on a four-point scale.Results 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. Conclusion Unprepared patients produce variable and often substantial volumes of urine during intravesical chemotherapy. There was a signi®cant 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 ef®cacy of treatment.

Epirubicin and meglumine γ‐linolenic acid

“…One study has reported the potential benefit, in terms of increasing intravesical drug concentration by reducing urine production, of desmopressin administration prior to mitomycin C treatment. However, data on improvements in actual cytotoxicity were not presented 30. Anthracyclines are weak bases: Epirubicin has a pKa of 7.7; thus, predominantly, it is charged neutrally and is lipophilic at alkaline pH but is charged positively at acid pH.…”

Investigational therapies for non-muscle invasive bladder cancer

“…A 6-h fasting period prior to instillation, reported to decrease urine volume and prevent 20% of drug dilution, is currently recommended by the European Association Urology guidelines for NMIBC [80]. Cliff and colleagues reported a 38% increase in intravesical mitomycin concentration following the administration of 0.2 mg oral desmopressin 1 h prior to instillation [81]; however, care must be taken in patients with cardiac failure or hyponatremia, and widespread use has not gained acceptance. Alkalinizing the urine with oral bicarbonate has also been shown to improve MMC drug stability, cellular uptake, and muscle penetration [78].…”

Intravesical Treatments of Bladder Cancer: Review

“…pH also affects the antitumor activity, e.g., MMC is more active at acidic pH in monolayer cultures (but no pH dependent-effect in 3-dimensional cultures) ( 69 ), epirubicin is more active at alkaline pH (8.0) than at lower pH (6.0) ( 70 ). The urine production rate and residual urine volume can be altered by patients’ hydration status, e.g., dehydration for 6 hr decreased the average volume of urine production from 209 to 143 ml, which is further reduced to 103 ml by co-administering an antidiuretic desmopressin ( 71 ).…”