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Clinical pharmacokinetics of high-dose mitomycin C

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Summary

The pharmacokinetic profile of high-dose mitomycin C was determined in blood plasma and urine of twelve patients with advanced malignancies in a program including autologous bone marrow transplantation. A total dose of 60 mg/m2 was given, either as a single 60-min infusion or divided into infusions of 30 mg/m2 on each of 2 days or 15 mg/m2 on each of 4 days. One group was given 15-min infusions. Samples of blood plasma and urine were analyzed by high-performance liquid chromatography. Drug concentrations in plasma followed a biphasic pattern, with a terminal elimination half-life of 45 min. This half-life value and other parameters were unaffected by dose level, infusion time, and repeated doses. The lower peak plasma concentrations following 30 mg/m2 given as 60-min infusions compared to the same dose given over 15 min may have accounted for a dramatic drop in the incidence of a severe hemorrhagic colitis. Mitomycin C was excreted in urine at about the same rate as it was eliminated from plasma, but a larger percentage of the dose appeared in urine after 15-min infusions than after 60-min infusions. The pharmacokinetic profile, together with clinical observations, suggests that the dose-limiting toxicity of mitomycin C may be related to peak drug levels, and that both these levels and the toxicity are lessened as the infusion time is increased.

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Authors and Affiliations

  1. Division of Oncology, Department of Internal Medicine, Wayne State University, School of Medicine, 48201, Detroit, MI, USA

    Rudolf B. Schilcher, John D. Young, Voravit Ratanatharathorn, Chatchada Karanes & Laurence H. Baker

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  1. Rudolf B. Schilcher
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  2. John D. Young
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  3. Voravit Ratanatharathorn
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  4. Chatchada Karanes
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  5. Laurence H. Baker
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Schilcher, R.B., Young, J.D., Ratanatharathorn, V. et al. Clinical pharmacokinetics of high-dose mitomycin C. Cancer Chemother. Pharmacol. 13, 186–190 (1984). https://doi.org/10.1007/BF00269026

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  • DOI: https://doi.org/10.1007/BF00269026

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