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. 1982 Feb;45(2):282–285. doi: 10.1038/bjc.1982.44

The penetration of misonidazole into a mature structural cartilage.

A J Langler, R D Bugden, P Gibson
PMCID: PMC2010886  PMID: 7059476

Abstract

Mature cartilage may be expected to contain populations of hypoxic cells as a result of the tissues lack of direct vascularization and structure; it may therefore be at risk from possible radiosensitization. The hypoxic-cell radiosensitizing drug misonidazole Ro-07-0582 (MISO) was administered i.v. to mature New Zealand White rabbits at a dose of 100 mg/kg, and the resulting drug concentrations in both blood and ear-cartilage samples measured by HPLC. Samples were taken at regular intervals up to 4 h after administration of MISO. Blood concentrations of MISO rose rapidly to 240 microgram/ml within 5 min of administration, before falling steadily, with a t1/2 of 45 min. Cartilage levels reached a peak of 70% of the blood levels approximately 30 min after administration. The levels of MISO then fell, with a t1/2 of 44 min.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ash D. V., Smith M. R., Bugden R. D. Distribution of misonidazole in human tumours and normal tissues. Br J Cancer. 1979 May;39(5):503–509. doi: 10.1038/bjc.1979.93. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Brown J. M., Workman P. Partition coefficient as a guide to the development of radiosensitizers which are less toxic than misonidazole. Radiat Res. 1980 Apr;82(1):171–190. [PubMed] [Google Scholar]
  3. CHURCHILL-DAVIDSON I., SANGER C., THOMLINSON R. H. Oxygenation in radiotherapy. II. Clinical application. Br J Radiol. 1957 Aug;30(356):406–422. doi: 10.1259/0007-1285-30-356-406. [DOI] [PubMed] [Google Scholar]
  4. Denekamp J., Fowler J. F. Radiosensitization of solid tumors by nitroimidazoles. Int J Radiat Oncol Biol Phys. 1978 Jan-Feb;4(1-2):143–151. doi: 10.1016/0360-3016(78)90130-x. [DOI] [PubMed] [Google Scholar]
  5. Denekamp J., Michael B. D., Harris S. R. Hypoxic cell radiosensitizers: comparative tests of some electron affinic compounds using epidermal cell survival in vivo. Radiat Res. 1974 Oct;60(1):119–132. [PubMed] [Google Scholar]
  6. Dische S., Saunders M. I., Lee M. E., Adams G. E., Flockhart I. R. Clinical testing of the radiosensitizer Ro 07-0582: experience with multiple doses. Br J Cancer. 1977 May;35(5):567–579. doi: 10.1038/bjc.1977.90. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Flockhart I. R., Large P., Troup D., Malcolm S. L., Marten T. R. Pharmacokinetic and metabolic studies of the hypoxic cell radiosensitizer misonidazole. Xenobiotica. 1978 Feb;8(2):97–105. doi: 10.3109/00498257809060388. [DOI] [PubMed] [Google Scholar]
  8. Gangji D., Poplack D. G., Schwade J., Wood J. H., Strong J. M. Misonidazole blood and cerebrospinal fluid kinetics in monkeys following intravenous and intrathecal administration. Eur J Cancer. 1981 Jan;17(1):29–34. doi: 10.1016/0014-2964(81)90208-5. [DOI] [PubMed] [Google Scholar]
  9. Gray A. J., Dische S., Adams G. E., Flockhart I. R., Foster J. L. Clinical testing of the radiosensitiser Ro-07-0582. I. Dose tolerance, serum and tumour concentrations. Clin Radiol. 1976 Apr;27(2):151–157. doi: 10.1016/s0009-9260(76)80137-7. [DOI] [PubMed] [Google Scholar]
  10. McNally N. J., Denekamp J., Sheldon P. W., Flockhart I. R. Hypoxic cell sensitization by misonidazole in vivo and in vitro. Br J Radiol. 1978 Apr;51(604):317–318. doi: 10.1259/0007-1285-51-604-317. [DOI] [PubMed] [Google Scholar]
  11. McNally N. J., Denekamp J., Sheldon P., Flockhart I. R., Stewart F. A. Radiosensitization by misonidazole (Ro 07-0582). The importance of timing and tumor concentration of sensitizer. Radiat Res. 1978 Mar;73(3):568–580. [PubMed] [Google Scholar]
  12. Pedersen J. E., Smith M. R., Bugden R. D., Peckham M. J. Distribution and tumour cytotoxicity of the radiosensitizer misonidazole (Ro-07-0582) in C57 mice. Br J Cancer. 1979 Apr;39(4):429–433. doi: 10.1038/bjc.1979.76. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Sheldon P. W., Hill S. A. Hypoxic cell radiosensitizers and local control by X-ray of a transplanted tumour in mice. Br J Cancer. 1977 Jun;35(6):795–808. doi: 10.1038/bjc.1977.121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Silver I. A. Measurement of pH and ionic composition of pericellular sites. Philos Trans R Soc Lond B Biol Sci. 1975 Jul 17;271(912):261–272. doi: 10.1098/rstb.1975.0050. [DOI] [PubMed] [Google Scholar]
  15. Stratford I. J., Adams G. E. The toxicity of the radiosensitizer misonidazole towards hypoxic cells in vitro: a model for mouse and man. Br J Radiol. 1978 Sep;51(609):745–746. doi: 10.1259/0007-1285-51-609-745. [DOI] [PubMed] [Google Scholar]
  16. Tushan F., Rodnan G. P., Altman M., Robin E. D. Anaerobic glycolysis and lactate dehydrogenase (LDH) isoenzymes in articular cartilage. J Lab Clin Med. 1969 Apr;73(4):649–656. [PubMed] [Google Scholar]
  17. Urtasun R. C., Band P., Chapman J. D., Rabin H. R., Wilson A. F., Fryer C. G. Clinical phase I study of the hypoxic cell radiosensitizer RO-07-0582, a 2-nitroimidazole derivative. Radiology. 1977 Mar;122(3):801–804. doi: 10.1148/122.3.801. [DOI] [PubMed] [Google Scholar]
  18. White R. A., Workman P., Freedman L. S., Owen L. N., Bleehen N. M. The pharmacokinetics of misonidazole in the dog. Eur J Cancer. 1979 Oct;15(10):1233–1242. doi: 10.1016/0014-2964(79)90249-4. [DOI] [PubMed] [Google Scholar]
  19. Wiltshire C. R., Workman P., Watson J. V., Bleehen N. M. Clinical studies with misonidazole. Br J Cancer Suppl. 1978 Jun;3:286–289. [PMC free article] [PubMed] [Google Scholar]
  20. Workman P. Dose-dependence and related studies on the pharmacokinetics of misonidazole and desmethylmisonidazole in mice. Cancer Chemother Pharmacol. 1980;5(1):27–37. doi: 10.1007/BF00578559. [DOI] [PubMed] [Google Scholar]
  21. Workman P., Little C. J., Marten T. R., Dale A. D., Ruane R. J., Flockhart I. R., Bleehen N. M. Estimation of the hypoxic cell-sensitiser misonidazole and its O-demethylated metabolite in biological materials by reversed-phase high-performance liquid chromatography. J Chromatogr. 1978 May 1;145(3):507–512. doi: 10.1016/s0378-4347(00)81386-9. [DOI] [PubMed] [Google Scholar]

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