A PK-PD model-based assessment of sugammadex effects on coagulation parameters.

Abstract Exposure–response analyses of sugammadex on activated partial thromboplastin time (APTT) and prothrombin time international normalized ratio (PT(INR)) were performed using data from two clinical trials in which subjects were co-treated with anti-coagulants, providing a framework to predict these responses in surgical patients on thromboprophylactic doses of low molecular weight or unfractionated heparin. Sugammadex-mediated increases in APTT and PT(INR) were described with a direct effect model, and this relationship was similar in the presence or absence of anti-coagulant therapy in either healthy volunteers or surgical patients. In surgical patients on thromboprophylactic therapy, model-based predictions showed 13.1% and 22.3% increases in respectively APTT and PT(INR) within 30 min after administration of 16 mg/kg sugammadex. These increases remain below thresholds seen following treatment with standard anti-coagulant therapy and were predicted to be short-lived paralleling the rapid decline in sugammadex plasma concentrations.