Vergin H, Bishop-Freudling G B, Miczka M, Nitsche V, Strobel K, Matzkies F
Arzneimittelforschung. 1985;35(10):1591-5.
An intraindividual comparative single-dose study was carried out under carefully controlled conditions on 12 healthy volunteers in order to establish the bioavailability of trans-4-(2-amino-3,5-dibromobenzyl)-amino-cyclohexanol (ambroxol) the active principle of newly developed tablets and drops, in comparison to a commercial i.v. preparation. In an additional single-dose, cross-over study on 12 healthy volunteers the bioequivalence of ambroxol was investigated after administration of a newly developed vs. a commercial dose-equivalent, sustained-release dosage form. Following off-line derivatisation using formaldehyde to the corresponding tetrahydroquinazoline compound, ambroxol was assayed from plasma by high-performance liquid chromatography. A 2-compartment model was taken as a basis for the calculation of the plasma concentration curves and the pharmacokinetic parameters following intravenous injection of the drug. After i.v. administration, the terminal elimination half-life, the apparent volume of distribution and the total plasma clearance were determined to be 3.72 h, 1.52 l/kg and 565 ml/min, respectively. From the tablet and drop formulations the systemic availabilities were calculated to 73 and 81%, respectively; the mean transit times were determined to be 6.8 and 5.4 h, respectively. Both sustained-release dosage forms investigated are bioequivalent.
在精心控制的条件下，对12名健康志愿者进行了一项个体内比较单剂量研究，目的是确定新开发的片剂和滴剂的活性成分反式-4-(2-氨基-3,5-二溴苄基)-氨基环己醇（氨溴索）与市售静脉制剂相比的生物利用度。在另一项针对12名健康志愿者的单剂量交叉研究中，研究了新开发的与市售剂量等效的缓释剂型给药后氨溴索的生物等效性。使用甲醛将其离线衍生化为相应的四氢喹唑啉化合物后，通过高效液相色谱法从血浆中测定氨溴索。以二室模型为基础计算静脉注射药物后的血浆浓度曲线和药代动力学参数。静脉给药后，终末消除半衰期、表观分布容积和总血浆清除率分别确定为3.72小时、1.52升/千克和565毫升/分钟。从片剂和滴剂制剂中计算出的全身利用率分别为73%和81%；平均通过时间分别确定为6.8小时和5.4小时。所研究的两种缓释剂型具有生物等效性。
