Abstract
In a previous report it was suggested that the total body clearance of mitomycin C (MMC) was different after single agent treatment compared to combination chemotherapy. This suggestion was based on recalculations to one dose level. In the present study a fixed dose of 10 mg/m2 was used. Seven patients on single agent MMC and eight on combination chemotherapy were studied. Terminal half-life varied from 25 to 78 mm, volume of distribution from 7 to 73 l/m2, total body clearance from 11 to 56 l/h per m2, and area under the plasma concentration-time curve (AUC) from 177 to 933 μg/h per 1. Total body clearance was significantly higher and AUC significantly lower in patients on combination chemotherapy. The cause of this difference was not investigated.
Key words: Pharmacokinetics, Mitomycin C, Combination chemotherapy
References
- 1.Buice RG, Niell HB, Sidhu P, Gurley BJ (1984) Pharmacokinetics of mitomycin C in non-oat cell carcinoma of the lung. Cancer Chemother Pharmacol 13:1–4 [DOI] [PubMed] [Google Scholar]
- 2.Doll DC, Weiss RB, Issell BF (1985) Mitomycin: ten years after approval for marketing J Clin Oncol 3:276–286 [DOI] [PubMed] [Google Scholar]
- 3.den Hartigh J, van Oort WJ, Bocken MCYM, Pinedo HM (1981) High performance liquid chromatography determination of the antitumor agent mitomycin C in human blood plasma. Anal Chim Acta 127:47–53 [Google Scholar]
- 4.den Hartigh J, McVie JG, van Oort WJ, Pinedo HM (1983) Pharmacokinetics of mitomycin C in humans Cancer Res 43:5017–5021 [PubMed] [Google Scholar]
- 5.den Hartigh J, Voortman G, van Oort WJ, Pinedo HM, Weenen H (1983) Binding of mitomycin C to red blood cells and plasma proteins. Proc ECCO 2:15 [Google Scholar]
- 6.van Hazel GA, Scott M, Rubin J (1983) Pharmacokinetics of mitomycin C in patients receiving the drug alone or in combination. Cancer Treat Rep 67:805–810 [PubMed] [Google Scholar]
- 7.Hu E, Howell SB (1983) Pharmacokinetics of intraarterial mitomycin C in humans Cancer Res 43:4474–4477 [PubMed] [Google Scholar]
- 8.Kerpel Fronius S, Verweij J, Stuurman M, Lelieveld, P, Pinedo HM (1986) Pharmacokinetics of mitomycin C given to Wistar rats alone in combination or after induction of microsomal drug metabolism (in press) [DOI] [PubMed]
- 9.Schilcher RB, Young JD, Ratanatharathorn V, Karanes C, Baker LH (1984) Clinical pharmacokinetics of high dose mitomycin C. Cancer Chemother Pharmacol 13:186–198 [DOI] [PubMed] [Google Scholar]
- 10.Verweij J, Boven E, van der Meulen J, Pinedo HM (1984) Recovery from mitomycin C induced haemolytic uraemic syndrome. A case report. Cancer 54:2878–2881 [DOI] [PubMed] [Google Scholar]
- 11.Wakaki S, Marumo H, Tomioka K (1958) Isolation of new fractions of antitumor mitomycins. Antibiot Chemother 8:228–240 [PubMed] [Google Scholar]