Pharmacokinetics of Recombinant Human Antithrombin in Delivery and Surgery Patients With Hereditary Antithrombin Deficiency. (May 2014)

• Record Type: Journal Article
• Authors: DeJongh, Joost; Frieling, Johan; Lowry, Simon; Drenth, Henk-Jan
• Is Part Of: Clinical and applied thrombosis/hemostasis. Volume 20:Number 4(2014:May)
• Page Start: 355
• Page End: 364
• Publication Date: 2014-05
• Subjects: recombinant antithrombin -- dosing -- model validation -- population pharmacokinetics; Hemostasis -- Periodicals; Thrombosis -- Periodicals; 616.13
• DOI: 10.1177/1076029613516188
• Languages: English
• ISSNs: 1076-0296

Abstract

Population pharmacokinetic (PK) analyses were conducted to refine dosing recommendations for recombinant human anti-thrombin therapy in surgery and delivery patients with hereditary antithrombin deficiency (HD). Single-dose PK data from patients with HD and nonlinear mixed-effects modeling were used to devise a dosing regimen to target antithrombin (AT) activity levels between 80% and 120% of normal. External validation with data from a phase 3 trial confirmed the correctness of a covariate-free model for surgery patients, but dosing adjustment was necessary for delivery patients. After different covariates were tested, the model was updated to incorporate the influential covariate, delivery . Simulations were used to develop a therapeutic drug-monitoring scenario that results in steady state AT activity levels within the target range as quickly as practically feasible. Data from a second clinical trial provided additional external validation and confirmed the accuracy of the dosing model for both groups of patients.