Bioavailability of opipramol from a film-coated tablet, a sugar-coated tablet and an aqueous solution in healthy volunteers.
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.
Kees
Frieder
F
Department of Pharmacology, University of Regensburg, Regensburg, Germany. Frieder.Kees@chemie.uni-regensburg.de
Jehkul
Andreas
A
Bucher
Michael
M
Mair
Georg
G
Kiermaier
Josef
J
Grobecker
Horst
H
D000328:Adult; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D001711:Biotransformation; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D008297:Male; D009888:Opipramol / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019999:Pharmaceutical Solutions; D013608:Tablets, Enteric-Coated
D000929:Antidepressive Agents, Tricyclic; D019999:Pharmaceutical Solutions; D013608:Tablets, Enteric-Coated; D009888:Opipramol