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Behavior and resorption of mitomycin C following multiple intravesical administrations
P J van Helsdingen1, E A de Bruijn, H P Sleeboom
1Department of Urology, Leyenburg Teaching Hospital, The Netherlands.
Abstract:
Although several pharmacological data of intravesical mitomycin C (MMC) are available now, data about resorption following subsequent intravesical instillations with different instillation times are lacking. We have analyzed MMC concentrations in blood plasma and urine following eight subsequent instillations, with 0.5- and 1.0-h instillation times. The relationships between urinary pH, urinary MMC concentrations, and MMC blood plasma concentrations were determined, as well as the stability of MMC in urine at pH 5-8 at 37 degrees C. An average of 40.3 and 46.4% of the total parent drug was recovered for the 0.5- and 1.0-h instillations, respectively. Blood plasma concentrations of MMC could be measured in nearly all patients and were independent of instillation times, urine concentration, or urinary pH. Resorption of MMC and recovery was stable during eight subsequent instillations. It was demonstrated that MMC can be degradated in urine at physiological conditions (pH less than 6; 37 degrees C). However, neither an influence of prolongation of the instillation time on MMC recovery from urine, nor a significant correlation between urinary pH and urinary MMC concentrations could be demonstrated. Since MMC can be degradated at pH less than 6 within 0.5 h, buffering of instillation fluids containing MMC is recommended. Reuse of instilled MMC, therefore, cannot be advised.
Insights
This study investigated mitomycin C (MMC) resorption during repeated bladder instillations. Findings show stable MMC absorption and recovery, but degradation in acidic urine necessitates buffering for optimal efficacy.
Area of Science:
- Pharmacology
- Urology
- Drug Metabolism
Background:
- Intravesical mitomycin C (MMC) is used for bladder cancer treatment.
- Limited data exists on MMC resorption and stability with varying instillation times during repeated treatments.
Purpose of the Study:
- To analyze MMC concentrations in plasma and urine after repeated intravesical instillations.
- To determine the impact of different instillation times (0.5 and 1.0 hours) on MMC resorption.
- To assess MMC stability in urine under physiological conditions and its relationship with urinary pH.
Main Methods:
- Eight subsequent intravesical MMC instillations were performed with 0.5- and 1.0-hour durations.
- MMC concentrations were measured in blood plasma and urine.
- Urinary pH and MMC stability in urine at 37°C (pH 5-8) were analyzed.
Main Results:
- Average urinary recovery was 40.3% (0.5h) and 46.4% (1.0h).
- Plasma MMC concentrations were measurable and independent of instillation time, urine concentration, or pH.
- MMC recovery remained stable across eight instillations.
- MMC degraded in urine at pH < 6 and 37°C.
Conclusions:
- Repeated intravesical MMC instillations show stable resorption and recovery.
- Prolonging instillation time did not significantly affect MMC recovery.
- MMC degradation in acidic urine (pH < 6) suggests buffering of instillation solutions is recommended.
- Reuse of instilled MMC is not advised due to potential degradation.
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