Comparison of tranexamic acid pharmacokinetics after intra-articular and intravenous administration in rabbits

Tranexamic Acid [TXA] is commonly administered in total knee arthroplasty for reducing blood loss. There has been a growing interest in the topical use of TXA except intravenous use for prevention of bleeding in TKA. The aim of this study was to develop and validate a HPLC-MS method to detect TXA and apply to compare the pharmacokinetic profile of TXA after intravenous [IV] and topical intra-articular [IA] application of TXA at a dose of 20 mg/kg in rabbits. In order to prove intra-articular administration is better than that of intravenous administration from the point of rabbit pharmacokinetic. Two groups of rabbits [n=6/group] respectively received TXA intra-articularly or intravenously. Blood samples were collected at scheduled time. The concentration of TXA in plasma was determined by a validated HPLC-MS method. Excellent linearity was found between 0.015 and 70.0microg/ml with a lower limit of quantitation [LLOQ]of 0.015microg/ml [r>0.99]; moreover, all the validation data including accuracy and precision [intra- and inter-day] were all within the required limits. The pharmacokinetic parameters in IA and IV group were: C[max]: 30.65+/-3.31 VS 54.05+/- 6.21 fig/ml [p<0.0l]; t[1/2]: 1.26+/-0.05 VS 0.68+/-0.13h [p<0.05]; AUC[0-t]: 42.98+/-7.73 VS 23.39+/-4.14microg/ml- h [p<0.0l], time above the minimum effective concentration [%T > MEC]: 1.5-2.2 VS 0.7-1.2h [p<0.05]. HPLC-MS method is suitable for TXA pharmacokinetic studies. The results demonstrated that topical intra-articular application of TXA showed a reduced peak plasma concentration and prolonged therapeutic drug level compared with intravenous TXA from the point of rabbit pharmacokinetic