Bioavailability investigation of two different oral formulations of citalopram, a so-called 'second generation' antidepressant drug

Citalopram (CAS 59729-33-8) belongs to the so-called 'second generation' antidepressant drugs and is used for the treatment of patients with major depression or other depressive disorders. In the present study, two different oral citalopram formulations (Citalopram-ratiopharm film-coated tablets as test preparation and tablets of a reference preparation distributed in Germany) were investigated in 20 healthy volunteers in order to prove bioequivalence between both preparations. A single 40 mg oral dose was administered according to an open, randomised, two-period cross-over design in the fasted state. Blood samples for determination of citalopram plasma concentrations were collected at pre-defined time points up to 168 h following drug administration. A wash-out period of 21 days separated both treatment periods. Citalopram plasma concentrations were determined by means of a validated HPLC method with fluorescence detection. Maximum plasma concentrations (C-max) of 34.77 ng/ml (test) and 34.42 ng/ml (reference) were achieved. Areas under the plasma concentration-time curve (AUC(0-infinity)) of 1,719.69 ng.h/ml (test) and 1,725.71 ng.h/ml (reference) were determined. The results showed nearly identical rate and extent of drug absorption. Also further pharmacokinetic Parameters were well comparable with each other. Thus, t(max) showed values of 3.29 h (test) and 3-77 h (reference). The plasma elimination half-life (t(1/2)) was 42.50 h (test) und 44.46 h (reference). Both primary target Parameters C-max and AUC(0-infinity). were tested Parametrically by analysis of variance (ANOVA). Bioequivalence between test and reference preparation was demonstrated since for both Parameters AUC and C-max the 90 % confidence intervals of the T/R-ratios of logarithmically trans formed data were in the generally accepted range of 80 %-125 %.