Effects of local hyperthermia on the pharmacokinetics of misonidazole in the anaesthetized mouse

Abstract

The effects of sodium pentobarbitone anaesthesia, the presence of a tumour, and local hyperthermia to a tumour-bearing leg, on the pharmacokinetics of MISO in the mouse are reported. Analysis of MISO and its metabolite Ro 05-9963 was by high-performance liquid chromatography. The plasma kinetics of MISO were largely unaffected by any of these treatments, but hyperthermia substantially reduced tumour concentrations of the drug. The effects of tumour site and size on unheated-tumour drug concentrations were also studied, and an increase in tumour size was shown to decrease tumour MISO levels, but to different degrees according to whether implanted in the leg or flank. Uniformity of MISO distribution throughout heated and unheated tumours was examined, and levels were found to be constant within tumours. The presence of a temperature detector in heated tumours did not affect their drug concentration.