Kivistö K T, Kallio A, Neuvonen P J
Department of Pharmacology, University of Turku, Finland.
Eur J Clin Pharmacol. 1994;46(4):345-9. doi: 10.1007/BF00194403.
Dexmedetomidine is a novel alpha 2-adrenoceptor agonist that may provide beneficial effects as premedication for anesthesia. The pharmacokinetics and pharmacodynamics of transdermal (TD) and intravenous (i.v.) dexmedetomidine were studied in nine healthy male subjects in a crossover trial. The TD preparation, containing 625 micrograms of dexmedetomidine base, was applied on the forehead and left in place for 12 h. The i.v. dose (2.0 micrograms.kg-1 as dexmedetomidine hydrochloride) was administered as an infusion over 5 min. Dose-normalized total AUC values were used to calculate dexmedetomidine bioavailability. The bioavailability of dexmedetomidine from the TD preparation was 51%. However, the bioavailability of dexmedetomidine released from the preparation was 88%. The mean terminal half-life was 3.1 h after i.v. and 5.6 h after TD administration. After TD administration, the mean maximal reductions in blood pressure (systolic/diastolic) and heart rate were 28/20 mmHg, and 19 beats.min-1. A sedative effect was obvious within 5 min and 1-2 h after i.v. and TD administration, respectively.
右美托咪定是一种新型的α2肾上腺素能受体激动剂，作为麻醉前用药可能具有有益作用。在一项交叉试验中，对9名健康男性受试者研究了经皮（TD）和静脉注射（i.v.）右美托咪定的药代动力学和药效学。将含有625微克右美托咪定碱的TD制剂贴于前额，留置12小时。静脉注射剂量（以盐酸右美托咪定计为2.0微克·kg-1）在5分钟内输注给药。使用剂量标准化的总AUC值计算右美托咪定的生物利用度。TD制剂中右美托咪定的生物利用度为51%。然而，制剂释放的右美托咪定的生物利用度为88%。静脉注射后平均终末半衰期为3.1小时，经皮给药后为5.6小时。经皮给药后，血压（收缩压/舒张压）和心率的平均最大降幅分别为28/20 mmHg和19次·min-1。静脉注射和经皮给药后，分别在5分钟内和1-2小时内出现明显的镇静作用。
