Summary
A new hypoxic cell radiosensitiser, Ro 03-8799 has been administered intravenously to human volunteers and its kinetic parameters derived from plasma and urine data. Good penetration of drug into tumour tissue is found, consistent with its large volume of distribution. The plasma clearance of this compound is rapid due to high metabolic and renal clearances. These parameters combine to produce an elimination half-life of 5.6 h, approximately half that of misonidazole, a well studied radiosensitiser. It is hoped that this decrease in total body exposure will also reduce the cumulative toxicity seen when misonidazole is administered repeatedly.
Similar content being viewed by others
References
Adams GE, Flockhart IR, Smithen CE, Straford IJ, Wardman P, Watts ME (1976) Electron-affinic sensitisation VII. A correlation between structures, one-electron reduction potentials and efficiencies of nitroimidazoles as hypoxic cell radiosensitisers, Radiat Res 67: 9–20
McNally NJ, Denekamp J, Sheldon P, Flockhart IR, Stewart FA (1978) Radiosensitisation by misonidazole. The importance of timing and tumour concentration of sensitisers. Radiat Res 73: 568–580
Dische S, Saunders MI, Lee ME, Adams GE, Flockhart IR (1977) Clinical testing of the radiosensitiser Ro 07-0582. Experience with multiple doses. Br J Cancer 35: 567–579
Smithen CE, Wardman P, Clarke ED (1980) Novel (nitro-1-imidazolyl)-alkanolamines as potential radiosensitisers with improved therapeutic proberties. In: Brady LW (ed) Radiation sensitisers: their use in the clinical management of cancer. Masson, New York, pp 22–32
Williams MV, Denekamp J, Minchington A, Stratford MRL (1982) In vivo assessment of basic 2-nitroimidazole radiosensitisers. Br J Cancer 46[1]: 127–137
Wardman P (1983) Molecular structure and biological activity of hypoxic cell radiosensitisers and hypoxic specific cytotoxins. In: Adams GE, Breccia A, Rimondi C (eds) Advanced topics of hypoxic cell radiosensitisers. Plenuim Press, New York
Bircher J, Kupfer A, Gikalov I, Preisig R (1976) Aminopyrene demethylation measured by breath analysis in cirrhosis. Clin Pharmacol Ther 20: 484–492
Malcolm SL, Lee A, Groves JK (1983) HPLC analysis of Ro 03-8799 in biological samples. J Chromatogr 273: 327–333
Francis RJ (1984) ELSMOS — An extended Least Squares modelling system in Fortran IV for mini-computer implementation. Comp Progr Biomed (in press)
Saunders MI, Dische S, Fermont D, Bishop A, Lenox-Smith I, Allen JG, Malcolm SL (1982) The radiosensitiser Ro 03-8799 and the concentrations which may be achieved in human tumours. Br J Cancer 46: 706
Lott RS, Hyton WL (1978) Estimation of creatinine clearances from serum creatinine concentration. Drug Intel Clin Pharmacol 12: 140–150
Schwade JG, Strong JM, Gangji D (1981) i.v. misonidazole report of initial clinical experience. Cancer Clin Trials 4: 33–39
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Allen, J.G., Dische, S., Lenox-Smith, I. et al. The pharmacokinetics of a new radiosensitiser, Ro 03-8799 in humans. Eur J Clin Pharmacol 27, 483–489 (1984). https://doi.org/10.1007/BF00549599
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00549599