Kees Frieder, Jehkul Andreas, Bucher Michael, Mair Georg, Kiermaier Josef, Grobecker Horst
Department of Pharmacology, University of Regensburg, Regensburg, Germany.
Arzneimittelforschung. 2003;53(2):87-92. doi: 10.1055/s-0031-1297077.
Opipramol (4-[3-(5H-dibenz[b,f]-azepine-5-yl)-propyl]-1-piperazine-ethanol dihydrochloride, CAS 315-72-0) is regarded as an anxiolytic compound with antidepressant properties, and it is one of the most frequently prescribed psychotropic drugs in Germany. In two open, randomized cross-over studies in 20 (study 1) and 18 (study II) healthy volunteers, the relative bioavailability of 50 mg opipramol-2HCl from a sugar-coated tablet was compared with an aqueous solution, and of 100 mg opipramol-2HCl from a newly developed film-coated tablet was compared with the sugar-coated tablet. The concentrations of opipramol were determined in plasma by high-performance liquid chromatography (HPLC) with photometric detection. The mean dose corrected kinetic parameters of opipramol were similar after administration of all formulations. The peak concentrations of opipramol were 13-15 ng ml-1 (study I) and 28 ng ml-1 (study II). They were achieved after 3 h. The area under the plasma concentration-time curve was about 170 ng ml-1 h (study I) and about 320 ng ml-1 h (study II). The terminal plasma half-life was 11 h. Bioequivalence was proven between sugar-coated tablet and aqueous solution, and between film-coated tablet and sugar-coated tablet, respectively. In addition, in study II the plasma concentrations and pharmacokinetic parameters of the metabolites opipramol N-oxide and deshydroxyethyl opipramol were determined.
奥匹哌醇（4-[3-(5H-二苯并[b,f]氮杂卓-5-基)-丙基]-1-哌嗪乙醇二盐酸盐，CAS 315-72-0）被视为一种具有抗抑郁特性的抗焦虑化合物，是德国最常处方的精神药物之一。在两项分别针对20名（研究I）和18名（研究II）健康志愿者的开放性随机交叉研究中，比较了糖衣片剂型的50 mg奥匹哌醇二盐酸盐与水溶液的相对生物利用度，以及新开发的薄膜包衣片剂型的100 mg奥匹哌醇二盐酸盐与糖衣片的相对生物利用度。采用带光度检测的高效液相色谱法（HPLC）测定血浆中奥匹哌醇的浓度。所有制剂给药后，奥匹哌醇的平均剂量校正动力学参数相似。奥匹哌醇的峰浓度分别为13 - 15 ng/ml（研究I）和28 ng/ml（研究II）。在3小时后达到这些峰浓度。血浆浓度-时间曲线下面积约为170 ng/ml·h（研究I）和约320 ng/ml·h（研究II）。终末血浆半衰期为11小时。分别证明了糖衣片与水溶液之间以及薄膜包衣片与糖衣片之间的生物等效性。此外，在研究II中还测定了代谢产物奥匹哌醇N-氧化物和去羟基乙基奥匹哌醇的血浆浓度和药代动力学参数。
