• Rolien Bosch, Marie-José van Lierop, de Kam Pieter-Jan PJ Clinical Research, Merck & Co., Inc., Kenilworth, NJ, United States., Annelieke C Kruithof, Jacobus Burggraaf, Rik de Greef, Sandra A G Visser, Amy O Johnson-Levonas, and Huub-Jan Kleijn.
• Quantitative Pharmacology & Pharmacometrics, MSD Oss B.V., Oss, The Netherlands. Electronic address: R.Bosch@lapp.nl.
• Eur J Pharm Sci. 2016 Mar 10; 84: 9-17.

AbstractExposure-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 30min after administration of 16mg/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. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

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