Pharmacokinetic comparison of two 40 mg tablet formulations of citalopram using a new amperometric detection technique.

Author(s): Al-Ghazawi M, Tutunji M, Mohsen M, Najjar S

Affiliation(s): Department of Biopharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, University of Jordan. alghazam@ju.edu.jo

Publication date & source: 2007-05, Int J Clin Pharmacol Ther., 45(5):300-6.

Publication type: Comparative Study; Randomized Controlled Trial

OBJECTIVES: To assess the bio-equivalence of two citalopram 40 mg tablet formulations (Lecital of the Jordan Sweden Medical and Sterilization Co. (JOSWE) as a test product, and Cipramil of Lundbeck (Denmark) as a reference product), and to develop a new high-performance liquid chromatography (HPLC) method using liquid-liquid extraction followed by addition of acid for the quantification of citalopram in human plasma. METHODS: A single-blind, randomized, single-dose, 2-treatment, 2-period, 2-sequence, crossover bioequivalence study with a 20-day washout period in 24 healthy volunteers. The drug was administered with 240 ml of water after 10-h overnight fasting. After dosing, serial blood samples were collected for a period of 192 h. Plasma harvested from blood was analyzed for citalopram by a novel method using HPLC coupled with an electrochemical detector. The limit of quantitation of citalopram was 1.493 ng/ml. Matrix-based calibration curves were linear over the range 1.493 - 80.640 ng/ml for citalopram. RESULTS: The average bioavailability and pharmacokinetic parameters of the two citalopram tablets were as follows: peak plasma concentration Cmax was 35.0 +/- 10.04 ng/ml and 33.4 +/-7.80 ng/ml for Lecital and Cipramil, respectively. The time to peak plasma concentrations tmax were 3.81 +/- 1.18 and 4.08 +/- 1.54 h, while the plasma half-life (t1/2) values were 54.0 +/- 7.50 and 54.7 +/- 10.6 h. The area under the plasma concentration-time profiles AUCo-t were 1,820 +/- 582 ng x h/ml and 1,660 +/- 510 ng x h/ml, whereas the AUC0-infinity were 2,010 +/- 663 ng x h/ml and 1,850 +/- 577 ng x h/ml for Lecital and Cipramil, respectively. The 90% confidence intervals for test/reference ratio were found within the acceptable limits of 80 - 125%, consequently no significant difference was found between the test and reference. CONCLUSION: Based on the pharmacokinetic and statistical results, it was concluded that Lecital 40 mg tablets of JOSWE is bioequivalent to Cipramil 40 mg tablets of Lundbeck (Denmark).