APPLICATION OF PHARMACOKINETIC DATA FROM HEALTHY-VOLUNTEERS FOR THE PREDICTION OF PLASMA-CONCENTRATIONS OF TRANEXAMIC ACID IN SURGICAL PATIENTS

The aim of this study was to investigate whether plasma concentrations of tranexamic acid in surgical patients during total hip replacement can be predicted from pharmacokinetic data from healthy volunteers, and whether therapeutic concentrations are sustained during the period of postoperative bleeding. Ten patients with normal kidney function received 10 mg/kg of tranexamic acid intravenously before surgery and another 10 mg/kg 3 hours later. Plasma concentration curves of tranexamic acid were computer-simulated, based on pharmacokinetic data from a volunteer study. Plasma concentrations in the patients were determined repeatedly and compared with the predicted values. Glomerular filtration rate was determined peroperatively as iohexol clearance. The blood loss was determined per- and postoperatively. The actual plasma concentrations of tranexamic acid were as predicted, or above, in all but two patients. These two were the youngest in the study, with the highest iohexol clearance; in both cases haemodilution was carried out and in one blood recovery with a cell saver was also used during surgery. A therapeutic level (> 10 mg/L) of tranexamic acid was maintained for approximately 8 hours, i.e. during the period of major bleeding. The plasma concentrations of tranexamic acid in surgical patients with normal kidney function can consequently be predicted from studies in healthy volunteers. Targeting of a therapeutic plasma concentration for the desired period of time is thus possible and can form the basis for a rational dosing of tranexamic acid.