Pharmacokinetic study of mitomycin C with emphasis on the influence of aging

Mitomycin C (MMC) at a dose of 8 mg/m2 was administered by short intravenous infusion to 14 cancer patients. All patients had normal renal, hepatic, cardiac and bone marrow functions. The plasma level of MMC, which was determined by high-performance liquid chromatography over a 24-h period after the infusion, fitted the 2-compartment model curve except for one patient. There was a significant correlation between the area under the time versus concentration curve (AUC) of MMC and the age of patients (r = 0.558, P < 0.05). Pharmacokinetic parameters in one of the older (a 69-year-old male) patients were extremely different from those of the other 13 patients. This patient experienced severe myelosuppression, probably due to the markedly increased AUC of MMC. Our results suggest that a patient's age has a significant influence on the pharmacokinetics of MMC in patients with normal major organ functions and that in some patients, MMC pharmacokinetics may be altered, possibly due to interpatient variation in the activation or metabolic pathway of MMC.