M. El Sadek, Samia M.Moustafa, Hussien O. Kadi, Abdul Moneim Ali Al-Hakami
The study was performed to compare the bioavailability of two Clopidogrel 75 mg tablet formulation (Plofixine from Asia- Syria as test formulation and Plavix from Sanofi-aventis-France, as reference formulation) in 6 male healthy volunteers. The study was conducted open with randomized two period crossover design and one week wash out period. Plasma samples were obtained over a 3hour interval. The carboxylic acid of Clopidogrel, major metabolite of Clopidogrel, was analyzed by LC-MS-MS, in the presence of clopidogrel-D4-carboxylic acid as internal standard. With plasma concentration vs. time curves, data obtained from this metabolite, the following pharmacokinetics parameters were obtained: Cmax, AUC0-t and Tmax.The mean AUC0-t and Cmax following oral administration of Plofexine and Plavix tablet, were 6119.84 , 5585.81 for AUC0-t and 4185.67, 3913.17ng/ml for Cmax respectively. The average time required to attain maximum plasma concentration ( Tmax) was 1.1and 0.997 hours for Plofexine and Plavix respectively, indicating that, the mean values were found to be similar for both the reference and test product and the value was 1.0 h. The 90% confidence intervals were 95-125% for AUC0-t, and 85-133% for Cmax. According to the 90% confidence intervals for the AUC0-t and Cmax proposed by US Food and Drug Administration, it was concluded that Plofexine 75 mg tablet was bioequivalent to Plavix 75 mg tablet for the extent of absorption, and not bioequivalent for the rate of absorption. According to some regional regulation such as GCC regulations on Drug Bioequivalence, the two products could be considered bioequivalent in the rate and extent of absorption too. The method of analysis which used was simple and suitable to evaluate the bioequivalence and clinical pharmacokinetic of clopidogrel.
Share this article