Effects of heat exposure in a Finnish sauna on the pharmacokinetics and metabolism of midazolam

Abstract

Objective: The effect of short-term heat exposure in a Finnish sauna on hepatic first-pass metabolism and the capacity to metabolize midazolam were studied in a crossover trial. Midazolam oral (15 mg) and intravenous (0.05 mg.kg-1) was given to 6 healthy young male volunteers, in random order, during a control session and a sauna bathing session (temperature 85-100 degrees C, relative humidity 25-30%). Blood samples for the determination of plasma midazolam and alpha-hydroxy midazolam concentrations were taken for 6 h after drug administration.

Results: After oral administration, the bioavailability and clearance of midazolam were not affected by sauna bathing, nor was there a significant difference in alpha-hydroxy midazolam plasma concentration or the alpha-hydroxy midazolam/midazolam AUC-ratio between the sessions. Midazolam Cmax was increased and its t1/2 beta was prolonged during the sauna session, but the clinical relevance of the findings appears to be modest. The pharmacokinetics of intravenous midazolam were not affected by sauna bathing.

Conclusions: Short-term heat exposure may not affect the first-pass metabolism or hepatic capacity to metabolize midazolam.