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 (Cmax), of 34.77 ng/ml (test) and 34.42 ng/ml (reference) were achieved. Areas under the plasma concentration-time curve (AUC0-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, tmax showed values of 3.29 h (test) and 3.77 h (reference). The plasma elimination half-life (t1/2) was 42.50 h (test) und 44.46 h (reference). Both primary target parameters Cmax and AUC0-infinity were tested parametrically by analysis of variance (ANOVA). Bioequivalence between test and reference preparation was demonstrated since for both parameters AUC and Cmax the 90 % confidence intervals of the T/R-ratios of logarithmically transformed data were in the generally accepted range of 80 %-125 %.
Gschwend
Michael H
MH
Pharmakin GmbH, Gesellschaft für Pharmakokinetik, Ulm Germany. michael.gschwend@pharmakin.de
Richter
Jutta
J
Sennewald
Regina
R
Guserle
Richard
R
Renner
Jürgen
J
Martin
Wolfgang
W
D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002138:Calibration; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D015283:Citalopram / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004355:Drug Stability; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011786:Quality Control
D018687:Antidepressive Agents, Second-Generation; D015283:Citalopram