title: Population pharmacokinetics of tranexamic acid in adults undergoing cardiac surgery with cardiopulmonary bypass.
abstract: BACKGROUND
  Interest in antifibrinolytic tranexamic acid (TA) has grown since the widespread removal of aprotinin, but its dosing during cardiac surgery is still debated. The objectives of this study were to investigate the population pharmacokinetics (PK) of TA given with either low- or high-dose continuous infusion schemes in adult cardiac surgery patients during cardiopulmonary bypass (CPB).
  
  
  METHODS
  Patients were randomized to receive either low-dose (10 mg kg(-1) followed by an infusion of 1 mg kg(-1) h(-1) throughout the operation, and 1 mg kg(-1) into the CPB) or high-dose (30 mg kg(-1), then 16 mg kg(-1) h(-1), and 2 mg kg(-1) into the CPB) TA. Serum TA concentrations were measured in 61 patients and the data were modelled using Monolix.
  
  
  RESULTS
  TA concentrations were 28-55 µg ml(-1) in the low-dose group and 114-209 µg ml(-1) in the high-dose group throughout surgery. TA PK was best described by a two-compartment open model. The main covariate effect was bodyweight, whereas the CPB did not influence the PK. Assuming a bodyweight of 70 kg, the population estimates were 4.8 litre h(-1) for clearance, 6.6 litre for the volume of the central compartment, 32.2 litre h(-1) for the diffusional clearance, and the peripheral volume of distribution was 10.8 litre.
  
  
  CONCLUSIONS
  The PK of TA was satisfactorily described by an open two-compartmental model, which was used to propose a dosing scheme suitable for obtaining and maintaining the desired plasma concentration in a stable and narrow range in cardiac surgery patients.
authors.affiliation: Laboratoire de Pharmacologie, UPRES EA220 and.
authors.forename: S
authors.initials: S
authors.lastname: Grassin-Delyle
authors.forename: B
authors.initials: B
authors.lastname: Tremey
authors.forename: E
authors.initials: E
authors.lastname: Abe
authors.forename: M
authors.initials: M
authors.lastname: Fischler
authors.forename: J C
authors.initials: JC
authors.lastname: Alvarez
authors.forename: P
authors.initials: P
authors.lastname: Devillier
authors.forename: S
authors.initials: S
authors.lastname: Urien
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000933:Antifibrinolytic Agents / Q000008:administration & dosage / Q000097:blood*; D001835:Body Weight / Q000502:physiology; D006348:Cardiac Surgical Procedures / Q000379:methods*; D002315:Cardiopulmonary Bypass; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007430:Intraoperative Care / Q000379:methods; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D014148:Tranexamic Acid / Q000008:administration & dosage / Q000097:blood*
chemical_list: D000933:Antifibrinolytic Agents; D014148:Tranexamic Acid
keywords: cardiopulmonary bypass; cardiovascular surgical procedures; pharmacokinetics; tranexamic acid