Schmekel B, Rydberg I, Norlander B, Sjöswärd K N, Ahlner J, Andersson R G
Dept. of Clinical Physiology, University Hospital, Linköping, Sweden.
Eur Respir J. 1999 Jun;13(6):1230-5. doi: 10.1034/j.1399-3003.1999.13f04.x.
Racemic R,S-salbutamol is taken to relieve bronchial constriction. Only the R-enantiomer has bronchodilating properties. The S-enantiomer has been proposed to cause in vitro bronchial hyperreactivity in guinea-pigs. Stereoselective elimination of salbutamol has been shown, with S-salbutamol being eliminated at a slower rate than R-salbutamol. This study questioned whether rates of stereoselective elimination were similar after oral or lung delivery, and whether the S:R ratio would increase after repeated inhalations in a situation resembling a common clinical use. Eighteen healthy volunteers received single-dose racemic salbutamol as a solution instilled in the trachea during anaesthesia, as inhaled micronized powder and/or as ingested tablets. Five volunteers inhaled repeated doses of racemic salbutamol. Concentrations in plasma and urine were measured using a technique which allowed chiral separation of samples with concentrations as low as 0.1 ng x mL(-1). The bioavailability of S-salbutamol was significantly higher than that of R-salbutamol after the different modes of administration. Stereoselective elimination was more pronounced after oral administration than after inhalation. Repeated inhalations resulted in successive increases in the S:R ratio as steady state was approached. In conclusion, the clinical consequences of increasing plasma concentrations of S-salbutamol need to be further assessed.
消旋的R,S-沙丁胺醇用于缓解支气管收缩。只有R-对映体具有支气管扩张特性。有人提出S-对映体可导致豚鼠体外支气管高反应性。已显示沙丁胺醇存在立体选择性消除，S-沙丁胺醇的消除速率比R-沙丁胺醇慢。本研究质疑口服或肺部给药后立体选择性消除速率是否相似，以及在类似常见临床应用的情况下重复吸入后S:R比值是否会增加。18名健康志愿者接受了单剂量消旋沙丁胺醇，剂型为麻醉期间经气管滴注的溶液、吸入用微粉化粉末和/或口服片剂。5名志愿者吸入了重复剂量的消旋沙丁胺醇。使用一种能对手性样品进行分离的技术测量血浆和尿液中的浓度，最低检测浓度为0.1 ng x mL(-1)。不同给药方式后，S-沙丁胺醇的生物利用度显著高于R-沙丁胺醇。口服给药后立体选择性消除比吸入给药更明显。接近稳态时，重复吸入导致S:R比值持续增加。总之，S-沙丁胺醇血浆浓度升高的临床后果需要进一步评估。
