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

Objectives: 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. Methods: 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 end-point was area under the curve from 2 to 60 minutes post-dose (AUC(2-60min)) for APTT and PT(INR). In vitro, the effects of sugammadex on APTT and PT were assessed in pooled normal human citrate plasma. Results: In subjects dosed with 4 and 16 mg/kg sugammadex, geometric mean ratios (treated vs. placebo) for AUC(2-60min) 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 mu g/mL (the mean maximum concentration reached therapeutically), the relative increases were 29% and 19%, respectively. Conclusions: 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.