Relationship between clinical parameters and pharmacokinetics of mitomycin C

Although the number of reports on mitomycin C (MMC) pharmacokinetics is increasing, data on possible relations between clinical parameters and pharmacokinetics are usually lacking. The present report concerns the results of a detailed study on this subject in 35 patients receiving MMC, either as a single agent or as a part of combination chemotherapy. MMC concentrations were determined by HPLC. T1/2 beta varied from 23 to 78 min, VD from 11 to 48 l/m2, Cl tot from 12 to 42 l/h per m2, and AUC from 138 to 1221 micrograms/h per l, confirming previously reported data. Infusion time, cholestasis, and urinary pH did not influence the pharmacokinetic data. There were no relations between other clinical data and pharmacokinetics, nor between AUC and bone marrow toxicity. An interaction between MMC and furosemide could not be excluded, but there was no interaction with other comedication. Consecutive pharmacokinetics in 6 patients showed consistent results. Because renal impairment does not alter MMC pharmacokinetics and renal excretion is not a major route of elimination, it is suggested that renal impairment does not call for dose adjustment.