Abstract

Dabigatran is an oral prodrug used for the prevention of venous thromboembolic events or stroke; a life-saving drug. The aim of present study was to ensure the in vivo performance of the dabigatran capsules marketed in Nepal. The study predicts in vivo study data of locally produced Dabigatran capsules (coded as Product A and Product B which are marketed without in vivo performance study using In Vitro In Vivo correlation (IVIVC) method. From predicted plasma drug concentration-time data, the Area Under the Curve (AUC), and maximum plasma drug concentration (Cmax) were determined for both test products A and B using numerical convolution technique. The analytical method used in this research is developed by National Medicine Laboratories. Acetonitrile and triethylamine (5mL Triethylamine in 1000 mL of water, adjust pH to 3.0 with orthophosphoric acid) is used as mobile phase in chromatographic system. The observed value of Cmax and AUC of the Reference Product was 105.63 ng/mL and 1708.28 ng*h/mL respectively. Similarly, Cmax and AUC of “Product A” from the convolution method was found to be 105.08 ng/mL, 1722.91 ng*h/mL while the Cmax and AUC of “Product B” was found to be 96.83 ng/mL, and 1583.40 ng*h/mL. The percentage prediction error (%PE) values for Cmax and AUC were found to be 0.52% and -0.85% for “Product A” and 9.09% and 7.89% for “Product B” respectively. The predicted error of AUC and Cmax are within the ±20% range for both local generic products (Product A and Product B). The rate and extent of absorption of test products were found to be similar in convolution method.

Keywords: IVIVC, Dabigatran, Bioequivalence, Convolution