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

Journal Article · Mon Mar 01 00:00:00 EST 1982 · Int. J. Radiat. Oncol., Biol. Phys.; (United States)

DOI:https://doi.org/10.1016/0360-3016(82)90654-X· OSTI ID:6718779

Coleman, C N ^[1]; Lee, W W; Constine, L S; Brown, J M

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1. Stanford Univ., CA

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 eliminaton. 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 radiosensitizaton. 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.

• OSTI ID: 6718779
• Journal Information: Int. J. Radiat. Oncol., Biol. Phys.; (United States), Vol. 8:3/4
• Country of Publication: United States
• Language: English

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