• Stanislas Grassin-Delyle, Michaela Semeraro, Frantz Foissac, Naim Bouazza, Haleema Shakur-Still, Ian Roberts, Jean-Marc Treluyer, and Saïk Urien.
• Centre d'Investigation Clinique P1419, INSERM, Hôpital Cochin-Necker, Université Paris Descartes, Sorbonne-Paris Cité, Paris, Bâtiment Imagine, 149 rue de Sèvres, 75 743 Paris cedex 15, France.
• Fundam Clin Pharmacol. 2019 Dec 1; 33 (6): 670-678.

AbstractTranexamic acid (TXA) is an antifibrinolytic drug that reduces surgical blood loss and death due to bleeding after trauma and post-partum haemorrhage. One key issue for treatment success is early administration. While usually given intravenously, oral and intramuscular use would be useful in specific circumstances. Therefore, an understanding of TXA pharmacokinetics when given via different routes is valuable. The aim of this study was to perform an individual participant data meta-analysis of pharmacokinetic studies with TXA given to healthy volunteers via different routes. We searched the following databases: PubMed, Web of Science, Wiley Online Library, Elsevier Science Direct and J-STAGE. Individual subject data were extracted when available, otherwise arithmetic means were used. A population pharmacokinetic model was developed using nonlinear mixed effect modelling. Seven studies were included in the analysis with data from 10 patients for the IV route, six patients for the IM route and 114 patients for the oral route. The pharmacokinetics was ascribed to a two-compartment model, and the main covariate was allometrically scaled bodyweight. Oral and IM bioavailabilities were 46 and 105%, respectively. For a 70 kg bodyweight, the population estimates were 7.6 L/h for clearance, 17.9 L for the volume of the central compartment, 2.5 L/h for the diffusional clearance and 16.6 L for the peripheral volume of distribution. Larger well-designed studies are needed to describe the pharmacokinetics of TXA when given IM or as an oral solution before these can be recommended as alternatives to IV.© 2019 Société Française de Pharmacologie et de Thérapeutique.

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