Thermophysiological responses to hyperthermic drugs: extrapolating from rodent to human

Abstract

This chapter focuses on the effects of hyperthermia on drug and chemical toxicity. In general, hyperthermia exacerbates the toxicity of many types of drugs and environmental toxicants. Using rodents to model the potential responses of humans to hyperthermic drugs is hampered by the unique differences in thermoregulatory ability and body mass. Because of their relatively large surface area:mass ratio, ambient temperature has a more profound influence on the potential hyperthermic effect of a drug in rodents. The relative increase in heat production (i.e., as a percentage of their basal metabolic rate) required to raise core temperature by 1 degrees C will increase with a decrease in body mass. The thermoregulatory response to methylenedioxymethamphetamine (MDMA) is used to illustrate the differences in thermoregulatory responses of rats and humans to a hyperthermic drug. Overall, the interaction between ambient temperature and drug-induced changes in body temperature is critical in the evaluation of hyperthermic-induced toxicity in rodent models.