Causes of apparent low levels of misonidazole in human tumours.

Although the concentration of misonidazole measured in human tumours may appear to be only 50--70% of the corresponding blood level, the concentration within the intra- and extracellular fluid of the tumour may be nearer 100% of the blood level. Causes for these apparent low levels of drug which have been investigated are: 1. Presence of fat in the tissue. 2. Presence of non-cellular material in the tissue. 3. Degradation of the drug by anaerobic metabolism after biopsy. An in vitro experiment to test the partitior fractionation study of the distribution of misonidazole showed that it is distributed mainly in the fluid compartment of the cell and that overall drug levels in tissue are related to the fluid content of the tissue. Serial measurements of misonidazole on tissue after removal from the body have shown that breakdown of the drug occurs when the tissue becomes anoxic. These results suggest that the concentration of misonidazole present within tumour cells is higher than the overall level measured for the tissue and that the enhancement ratio to be expected may therefore be higher also.