Population Pharmacokinetic Analysis of the New Oral Thrombin Inhibitor Dabigatran Etexilate (BIBR 1048) in Patients Undergoing Primary Elective Total Hip Replacement Surgery

摘要: Dabigatran etexilate (BIBR 1048) is an orally bioavailable double prodrug of the active principle dabigatran 953 ZW), which exerts potent anticoagulant and antithrombotic activity. The objective analysis was to develop a population pharmacokinetic model characterizing quantifying relationship between covariates parameters. A total 4604 BIBR ZW plasma concentrations, obtained from 287 patients after once- or twice-daily oral dosing for up 10 days surgery in dose range 12.5, 25, 50, 100, 150, 200, 300 mg 1048, were available analysis. All analyses performed with NONMEN V. Pharmacokinetics best described by 2-compartment model. data supported estimation different apparent first-order absorption rate constants (k(a)) clearances (CL/F) 0 1 2 surgery. Parameter estimates indicated flip-flop phenomenon. Age serum creatinine influenced k(a), whereas gastrin clearance, only 10, affected CL/F (P < .001). typical values patient 34.58 pmol/L clearance 76.16 mL/min 70.87 106.2 L/h on respectively. differences found pharmacokinetics during first 24 hours are most likely due alterations gastric motility pH following As consequence, reduced interindividual variability drug exposure increased. On days, disposition less variable.