Pharmacokinetics of methotrexate during regional hyperthermia in a pig model.

In the pig model, regional hyperthermia in the gluteus was combined with the infusion of 150 mg MTX over a period of 100-120 min. The pharmacokinetic data reveal that this approach is capable of simulating the situation that is necessary and achievable in medium-dose MTX therapy of human tumours. Under MTX infusion, serum levels in the region of 10(-5) M are attained. As an expression of a renal and hepatic MTX excretion, high levels of MTX are found both in the urine and in the bile. Especially high concentrations of MTX are found in the liver and kidney tissue. In the normothermic and hyperthermic muscle, very low MTX levels are found. The pharmacokinetic data obtained show that the selected model is suitable for the future investigation of the effect of regional hyperthermia and MTX on transplanted tumours.