This paper describes an investigation into the pharmacokinetic behavior of mitomycin C (MMC) in 36 patients receiving either single-agent chemotherapy (10 to 20 mg/sq m), or a combination regimen including MMC (5 to 10 mg/sq m).
A high-performance liquid chromatographic assay of MMC was applied for the analysis of plasma, urine, bile, and ascites fluid samples. The detection limit is 1 ng/ml sample. Most patients were given short-term i.v. infusion, although other methods of administration were used as well. Most plasma concentration-time curves fit a two-compartment model.
Pharmacokinetic parameters revealed large interindividual variations. Median terminal half-lives in single-agent chemotherapy and combination chemotherapy were 50 and 42 min, respectively. The apparent volume of the central compartment was 7 liters/sq m in both groups. The volume of distribution was 22 liters/sq m in single-agent chemotherapy, and 25 litres/sq m in combination chemotherapy. Linear regression analysis of the area under the plasma concentration-time curve versus the dose did not produce any evidence that the pharmacokinetics was dose dependent. However, differences were observed between patients receiving MMC alone and those on combination chemotherapy, in particular with regard to the total body clearance: 18 liters/hr/sq m for single-agent chemotherapy and 28 liters/hr/sq m for combination chemotherapy. Urinary recovery was limited to a maximum of 15% of the administered dose. In one patient studied, MMC was found to be present in the bile. There is evidence for enterohepatic circulation of MMC, and MMC was also found to penetrate into the ascites fluid.
Supported in part by a grant from the Koningin Wilhelmina Fonds (Grant THT 80-1) and in part by the Bristol Myers International Corporation.