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


CONCLUSIONS
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).
Al-Ghazawi
M
M
Department of Biopharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, University of Jordan. alghazam@ju.edu.jo
Tutunji
M
M
Mohsen
M
M
Najjar
S
S
D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D015283:Citalopram / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016001:Confidence Intervals; D018592:Cross-Over Studies; D004355:Drug Stability; D006207:Half-Life; D006801:Humans; D008297:Male; D012680:Sensitivity and Specificity; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013607:Tablets; D013810:Therapeutic Equivalency
D015283:Citalopram; D017367:Selective Serotonin Reuptake Inhibitors; D013607:Tablets