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.
Highlights
Summary.-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
It is necessary to check the effect of an anaesthetic in any system where it has been used, and the first part of the present paper describes our investigations into the effect of sodium pentobarbitone on the pharmacokinetics of MISO
The effect of this dose on MISO pharmacokinetics was investigated in nontumour-bearing mice
Summary
Summary.-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. The effects of tumour site and size on unheated-tumour drug concentrations were 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. It has been further demonstrated that this cytotoxicity is enhanced by hyperthermia both in vitro (Bleehen et al, 1976; Stratford & Adams, 1977) and in vivo in the mouse (Bleehen et al, 1977; GAeorge et al, 1977) This in vivo work in the mouse has involved anaesthetizing the animal, usually with sodium pentobarbitone. In this paper we report investigations into the effect of local hyperthermia on the pharmacokinetics of MISO by studying plasma and tumour concentrations of MISO and its 0-demethylated metabolite, Ro 05-9963. Leg tumours were produced by i.m. inoculation in the lower leg, and flank tumours by inoculation intradermally (i.d.) in the previously plucked skin of the flank
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