Vanakoski J, Idänpään-Heikkilä J J, Olkkola K T, Seppälä T
Department of Pharmacology and Toxicology, University of Helsinki, Finland.
Eur J Clin Pharmacol. 1996;51(3-4):335-8. doi: 10.1007/s002280050208.
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.
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.
Short-term heat exposure may not affect the first-pass metabolism or hepatic capacity to metabolize midazolam.
在一项交叉试验中，研究芬兰桑拿浴短期热暴露对肝脏首过代谢及咪达唑仑代谢能力的影响。6名健康年轻男性志愿者在对照期和桑拿浴期（温度85 - 100摄氏度，相对湿度25 - 30%），随机接受口服咪达唑仑（15毫克）和静脉注射咪达唑仑（0.05毫克/千克）。给药后6小时采集血样以测定血浆咪达唑仑和α-羟基咪达唑仑浓度。
口服给药后，桑拿浴对咪达唑仑的生物利用度和清除率无影响，各期之间α-羟基咪达唑仑血浆浓度或α-羟基咪达唑仑/咪达唑仑AUC比值也无显著差异。在桑拿浴期，咪达唑仑的Cmax升高，t1/2β延长，但这些结果的临床相关性似乎不大。静脉注射咪达唑仑的药代动力学不受桑拿浴影响。
短期热暴露可能不会影响首过代谢或肝脏代谢咪达唑仑的能力。
