Population pharmacodynamics in patients receiving tinzaparin for the prevention and treatment of deep vein thrombosis

Abstract

Changes of these magnitudes were not clinically important in pooled clinical trial safety and efficacy analyses. Body weight was not a significant covariate in the model supporting the observations in earlier well-defined trials, where tinzaparin was dosed on a weight basis (lU/kg). Clearance was not influenced by age, race or gender. The same model was applied to data obtained from a prospective, randomized, double-blind clinical trial comparing tinzaparin (4,500 IU) to enoxaparin (40 mg) once daily in patients undergoing total hip replacement. Model parameters were similar to those previously obtained supporting the extension of these results across dose and indication. Population analysis in patients with disease and heterogeneity indicated similar pharmacodynamics as in volunteers, supporting weight-based dosing and identified the dependence of clearance on obesity and severe renal function, although the magnitude of these effects are probably not clinically significant.