In this article, we will discuss Mitomycin (Mechanism of Action). So, let’s get started.
Mechanism of Action
Mitomycin inhibits the synthesis of deoxyribonucleic acid (DNA). The guanine and cytosine content correlates with the degree of mitomycin-induced cross-linking. At high concentrations of the drug, cellular RNA and protein synthesis are also suppressed.
There is insufficient data to characterize an exposure-response relationship or time course of pharmacodynamic response for mitomycin.
The systemic exposure of mitomycin following instillation of up to 60 mg of mitomycin as mitomycin into the pyelocalyceal system was evaluated pre-instillation and hourly for up to six hours post-instillation in six patients. The concentrations of mitomycin in plasma were variable and ranged from 2.43 to 12.80 ng/mL over the course of treatment; the mean Cmax was 6.24 ng/mL, which is estimated to be less than 1% of the expected Cmax after intravenous administration.
Following instillation into the pyelocalyceal system, mitomycin forms a semisolid gel which dissolves from normal kidney urine flow releasing mitomycin for up to 4 to 6 hours. Mitomycin is eliminated unchanged in the urine. Systemically absorbed mitomycin is rapidly cleared from the serum and approximately 10% is excreted unchanged in the urine.
Mitomycin is metabolized primarily in the liver, but metabolism occurs in other tissues as well. It is believed that the rate of clearance is inversely proportional to the maximal serum concentration because of saturation of the degradative pathways.