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Cancer Chemotherapy and Pharmacology

, Volume 14, Issue 2, pp 125–131 | Cite as

Clinical pharmacokinetics of oral CCNU (Lomustine)

  • Francis Y. F. Lee
  • Paul Workman
  • J. Trevor Roberts
  • Norman M. Bleehen
Original Articles Pharmacokinetics CNNU, Lomustine

Summary

The plasma pharmacokinetics of orally administered CCNU (130 mg/m2) were studied in four patients using reversed-phase high-performance liquid chromatography (HPLC) analysis. Parent CCNU was not detected in the plasma of any of the patients, probably due to complete conversion to monohydroxylated metabolites during the ‘first pass’ through liver and gut. However, two monohydroxylated metabolites, trans-4-hydroxy CCNU and cis-4-hydroxy CCNU, were found at high concentrations, the relative amounts being about 6 : 4. Peak concentrations of the metabolites were reached 2–4 h after administration and were remarkably similar for all four patients, the total being 0.8–0.9 μg/ml. The metabolites were also detected in a tumour biopsy. Plasma clearance half-lives of the two metabolites were similar in each patient but showed a two-fold variation between patients, from 1.3 to 2.9 h. These results suggest that the antitumour activity and systemic toxicity of CCNU when given orally are due mainly to its monohydroxylated metabolites. Finally, comparison with data obtained in vitro and in mice showed that the nitrosourea exposures in these patients were at the lower limit of those required for significant antineoplastic activity.

Keywords

Liquid Chromatography Cancer Research Lower Limit Peak Concentration Clinical Pharmacokinetic 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag 1985

Authors and Affiliations

  • Francis Y. F. Lee
    • 1
    • 2
  • Paul Workman
    • 1
    • 2
  • J. Trevor Roberts
    • 1
    • 2
  • Norman M. Bleehen
    • 1
    • 2
  1. 1.MRC UnitCambridgeUK
  2. 2.University Department of Clinical Oncology and RadiotherapeuticsCambridgeUK

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