Effects of a sauna on the pharmacokinetics and pharmacodynamics of midazolam and ephedrine in healthy young women

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Abstract
The effect of a sauna on the pharmacokinetics and pharmacodynamics of single doses of ephedrine 50 mg and midazolam 15 mg have been studied in 6 young healthy women in a placebo-controlled, double-blind study. The sauna (3 × 10 min; temperature 80–100°C; relative humidity 30–50%) modified the pharmacokinetics of both drugs: it retarded the absorption of midazolam estimated as Ka values, and it reduced the mean plasma midazolam concentrations at 2 h; ephedrine, was absorbed more rapidly and the maximum plasma concentration occurred earlier than in the control sessions. Changes in the pharmacodynamics due to the sauna were consistent with the pharmacokinetic findings: midazolam decreased flicker recognition and induced exophoria significantly less during the early sauna period than in the control session, whereas ephedrine made the volunteers subjectively more alert at that time. Later, at 2.5 and 3.5 h (1 h 20 min and 2 h 20 min after cessation of the sauna), and despite the equalisation of the plasma levels, midazolam caused significantly more exophoria after the sauna than in the control situation. This indicates an influence of a sauna on drug pharmacodynamics in the post-sauna adaptive phase. The results suggest that exposure to a sauna may alter both drug pharmacokinetics and pharmacodynamics.