The development of an oral prodrug, SR-2545, of the 2-nitroimidazole radiosensitizer SR-2508

C. Norman Coleman, William W. Lee, Louis S. Constine, J. Martin Brown

Research output: Contribution to journalArticle

Abstract

SR-2508, a 2-nitroimidazole radiosensitizer, is expected to be clinically superior to desmethylmisonidazole or misonidazole because of its lower lipophilicity with subsequent lower drug levels in neural tissue and more rapid plasma elimination. The intravenous route of administration will be optimal but oral drugs may be necessary. Since decreased lipophilicity will decrease oral absorption we have synthesized, and tested in mice, SR-2545, an acetate ester prodrug of SR-2508. In the liver there is complete first pass metabolism to parent drug with no prodrug detectable in the blood. Compared to an equal dose of oral SR-2508, the prodrug yields a more rapid, reproducible, plasma peak with twice the bioavailability, peak plasma concentration and radiosensitization. If oral preparations of SR-2508 are to be used in the clinic the prodrug, SR-2545, is likely to be superior to oral SR-2508.

Original languageEnglish (US)
Pages (from-to)431-434
Number of pages4
JournalInternational journal of radiation oncology, biology, physics
Volume8
Issue number3-4
DOIs
StatePublished - Jan 1 1982

Keywords

  • Pharmacology
  • Radiosensitizers

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Fingerprint Dive into the research topics of 'The development of an oral prodrug, SR-2545, of the 2-nitroimidazole radiosensitizer SR-2508'. Together they form a unique fingerprint.

  • Cite this