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

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• 作者：Rolien Bosch^a ; ¹ ; ^{R.Bosch@lapp.nl" class="auth_mail" title="E-mail the corresponding author} ; Marie-José ; van Lierop^a ; ² ; Pieter-Jan de Kam^b ; ³ ; Annelieke C. Kruithof^c ; Jacobus Burggraaf^c ; Rik de Greef^a ; ⁴ ; Sandra A.G. Visser^b ; ⁵ ; ^{sandra.visser@merck.com" class="auth_mail" title="E-mail the corresponding author} ; Amy O. Johnson-Levonas^d ; Huub-Jan Kleijn^a ; ⁴
• 关键词：Sugammadex ; Pharmacokinetics ; Pharmacodynamics ; APTT ; PT(INR) ; PK&ndash ; PD model
• 刊名：European Journal of Pharmaceutical Sciences
• 出版年：2016
• 出版时间：10 March 2016
• 年：2016
• 卷：84
• 期：Complete
• 页码：9-17
• 全文大小：611 K

文摘

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.