Bioavailability investigation of two different oral formulations of Tetrazepam.
Two different oral tetrazepam (CAS 10379-14-3) formulations (Tetrazepam-ratiopharm film-coated tablets as test preparation and tablets of a reference preparation marketed in France) were investigated in 20 healthy volunteers in order to prove bioequivalence between these preparations. A single 50 mg oral dose was given according to a randomised two-way crossover design in the fasted state. Blood samples for determination of tetrazepam plasma concentrations were collected at pre-defined time points up to 96 h following drug administration. A washout period of 14 days separated both treatment periods. Tetrazepam plasma concentrations were determined by means of a validated LC-MS/MS method. Values of 3873.08 ngh/ml (test preparation) and 3930.69 ngh/ml (reference preparation) for the parameter AUC0-infinity demonstrate an nearly identical extent of drug absorption. Maximum concentrations (Cmax) of 482.08 ng/ml and 465.14 ng/ml were achieved for test and reference preparation. Time to reach maximum plasma concentration (tmax) was 1.39 hours for both preparations. Cmax and AUC0-infinity-values were tested parametrically by an analysis of variance (ANOVA). Bioequivalence was concluded if the 90% confidence intervals of the T/R-ratios were in the range of 80%-125% for AUC0-infinity and 70%-143% for Cmax. Based on the results obtained in this study, bioequivalence between the test and the reference preparation was demonstrated.
Geister
U
U
Pharmakin GmbH, Gesellschaft für Pharmakokinetik, Ulm, Germany. ursugeis@pharmakin.de
Gaupp
M
M
Arnold
P
P
Schaarschmidt
D
D
Doser
K
K
D000284:Administration, Oral; D000328:Adult; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001569:Benzodiazepines; D001682:Biological Availability; D002138:Calibration; D002853:Chromatography, Liquid; D018592:Cross-Over Studies; D004355:Drug Stability; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D011786:Quality Control; D013608:Tablets, Enteric-Coated
D014151:Anti-Anxiety Agents; D013608:Tablets, Enteric-Coated; D001569:Benzodiazepines; C005245:tetrazepam