Effects of sugammadex on activated partial thromboplastin time and prothrombin time in healthy subjects

• Published in: International journal of clinical pharmacology and therapeutics Vol. 52; no. 3; p. 227
• Main Authors: De Kam, Pieter-Jan, Grobara, Peter, Prohn, Marita, Höppener, Floris, Kluft, Cornelis, Burggraaf, Jacobus, Langdon, Ronald B, Peeters, Pierre
• Format: Journal Article
• Language: English
• Published: Germany 01.03.2014
• Subjects: Adult; Cross-Over Studies; Dose-Response Relationship, Drug; Female; gamma-Cyclodextrins - adverse effects; gamma-Cyclodextrins - pharmacokinetics; gamma-Cyclodextrins - pharmacology; Humans; International Normalized Ratio; Male; Partial Thromboplastin Time; Prothrombin Time; Young Adult
• ISSN: 0946-1965
• DOI: 10.5414/CP201976

To assess the impact of sugammadex on activated partial thromboplastin time (APTT) and international normalized ratio for prothrombin time (PT(INR)) in healthy subjects and characterize the concentration-dependency of sugammadex effects on APTT and prothrombin time (PT) in normal human plasma in vitro. Eight healthy subjects (18 - 45 years of age) were administered intravenous doses of 4 mg/kg sugammadex, 16 mg/kg sugammadex, or placebo in a randomized, placebo-controlled, three period cross-over trial. The primary endpoint was area under the curve from 2 to 60 minutes post-dose (AUC2-60min) for APTT and PT(INR). In vitro, the effects of sugammadex on APTT and PT were assessed in pooled normal human citrate plasma. In subjects dosed with 4 and 16 mg/kg sugammadex, geometric mean ratios (treated vs. placebo) for AUC2-60min were 1.085 (95% confidence interval, 0.888 - 1.325) and 1.019 (0.868 - 1.195), respectively, for APTT, and 1.047 (0.904 - 1.213) and 1.096 (0.953 - 1.261), respectively, for PT(INR). At individual timepoints, mean APTT and PT(INR) increased by up to 22% after 16 mg/kg sugammadex compared with placebo. All such increases occurred within 30 minutes post-dose. Sugammadex was generally well tolerated. In the in vitro experiments, addition of sugammadex to plasma resulted in limited, concentration dependent increases in both APTT and PT. At 200 μg/mL (the mean maximum concentration reached therapeutically), the relative increases were 29% and 19%, respectively. Administration of sugammadex is associated with a dose-related, limited and transient prolongation of APTT and PT(INR) that is unlikely to be of clinical relevance.