Bioavailability of opipramol from a film-coated tablet, a sugar-coated tablet and an aqueous solution in healthy volunteers

• Published in: Arzneimittel-Forschung Vol. 53; no. 2; pp. 87 - 92
• Main Authors: KEES, Frieder, JEHKUL, Andreas, BUCHER, Michael, MAIR, Georg, KIERMAIER, Josef, GROBECKER, Horst
• Format: Journal Article
• Language: English
• Published: Aulendorf Cantor 01-01-2003
• Subjects: Adult; Antidepressive Agents, Tricyclic - administration & dosage; Antidepressive Agents, Tricyclic - adverse effects; Antidepressive Agents, Tricyclic - pharmacokinetics; Area Under Curve; Biological and medical sciences; Biological Availability; Biotransformation; Cross-Over Studies; Female; Humans; Male; Medical sciences; Opipramol - administration & dosage; Opipramol - adverse effects; Opipramol - pharmacokinetics; Pharmaceutical Solutions; Tablets, Enteric-Coated; Opipramol, aqueous solution, bioequivalence, film coated tablet, sugar-coated tablet; CAS 315-72-0; Insidon
• ISSN: 0004-4172; 1616-7066
• 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.