Heat exposure and drugs. A review of the effects of hyperthermia on pharmacokinetics.

Acute heat loading is encountered in several everyday situations, during physical exercise or work in a hot climate are just 2 examples. Special forms of heat exposure include different types of steam baths and saunas. External heating induces changes in haemodynamics, body fluid volume and blood flow distribution, which in turn may affect the pharmacokinetics of a drug and the therapeutic response. Documentation of the effects of heat exposure on the pharmacokinetics of drugs in humans is very limited, but based on the documentation some general conclusions can be drawn. The effects of external heating on absorption and elimination of those orally administered drugs which have been studied (e.g. midazolam, ephedrine, propranolol and tetracycline), have been minor. Systemic absorption of transdermally and subcutaneously administered drugs [insulin, nitroglycerin (glyceryl trinitrate) and nicotine] is in most cases enhanced by external heating, leading to higher plasma drug concentrations. In general, pharmacokinetic interactions between heat exposure and drug therapy are rare and limited to special situations, in which local blood flow (for example, over the skin) is enhanced many-fold because of hyperthermia. When pharmacodynamics are concerned, in most cases the probability of interactions is low, but in the treatment of malignant tumours hyperthermia may potentiate cytotoxic effects of drugs without enhancement of myelosuppressive effects.