The Clinical Pharmacology of Misonidazole in Radiation Therapy Oncology Group Trials
Because the effectiveness of a hypoxic cell sensitizer of the imidazole class depends directly on its concentration in serum and within the tumor, the pharmacologic distribution of these drugs is of extreme importance. Numerous reports including those originally of Adams and colleagues (1), McNally (2) and of Denekamp (3) have indicated as well as have the skin experiments of Dische and colleagues (4), that the enhancement ratio observable is closely tied to the concentration in tumor and serum. The concentrations versus effectiveness curve for misonidazole rises steeply so that enhancement ratios between 1.3 and 1.5 may be observed at concentrations as low as 25–30 μg/ml within tumor. For these reasons, the determination of concentration within tumor and serum, a more readily-measurable quantity, has been extremely important in the Phase I and II studies of the RTOG (5–9).
KeywordsHigh Performance Liquid Chromatography Roswell Park Memorial Institute Hypoxic Cell Enhancement Ratio High Performance Liquid Chromatography Method
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