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

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.