Pharmacokinetic and anti-tumor studies with the radiosensitizer misonidazole in dogs with spontaneous fibrosarcomas.

Nine dogs with spontaneous oral fibrosarcomas were given the radiosensitizer misonidazole (Ro-07-0582) In combination with orthovoltage radiotherapy. Although there appeared to be a trend toward greater disease-free survival of these animals as compared with a group of 13 dogs with similar tumors treated by orthovoltage x-rays alone, on analysis there was no significant difference. The plasma half-life and the volume of distribution of misonidazole were determined as 4.95 hours and 15.1 L/m2, respectively. In 3 dogs with evidence of misonidazole toxicosis, plasma concentrations at 4 hours after the dose exceeded 85 microgram/ml, and the areas under the concentration vs time curve for this first 10 hours were greater than 850 microgram.hr/ml.