lcholine-induced neuromuscular blockade (1 mg/kg) was compared with sugammadex (16 mg/kg, 3 minutes later) – induced recovery from rocuronium-induced neuromuscular blockade (1.2 mg/kg).
Time (minutes) from administration of rocuronium and sugammadex or succinylcholine to recovery of the T1 10%
In a pooled analysis the following recovery times for 16 mg/kg sugammadex after 1.2 mg/kg rocuronium bromide were reported:
Time (minutes) from administration of sugammadex at 3 minutes after rocuronium to recovery of the T4/T1 ratio to 0.9, 0.8 or 0.7
Renal impairment:
Two open label studies compared the efficacy and safety of sugammadex in surgical patients with and without severe renal impairment. In one study, sugammadex was administered following rocuronium induced blockade at 1-2 PTCs (4 mg/kg; N=68); in the other study, sugammadex was administered at reappearance of T2 (2 mg/kg; N=30). Recovery from blockade was modestly longer for patients with severe renal impairment relative to patients without renal impairment. No residual neuromuscular blockade or recurrence of neuromuscular blockade was reported for patients with severe renal impairment in these studies.
5.2 Pharmacokinetic properties
The sugammadex pharmacokinetic parameters were calculated from the total sum of non-complex-bound and complex-bound concentrations of sugammadex. Pharmacokinetic parameters as clearance and volume of distribution are assumed to be the same for non-complex-bound and complex-bound sugammadex in anaesthetised subjects.
Distribution:
The observed steady-state volume of distribution of sugammadex is approximately 11 to 14 litres in adult patients with normal renal function (based on conventional, non-compartmental pharmacokinetic analysis). Neither sugammadex nor the complex of sugammadex and rocuronium binds to plasma proteins or erythrocytes, as was shown in vitro using male human plasma and whole blood. Sugammadex exhibits linear kinetics in the dosage range of 1 to 16 mg/kg when administered as an IV bolus dose.
Metabolism:
In preclinical and clinical studies no metabolites of sugammadex have been observed and only renal excretion of the unchanged product was observed as the route of elimination.
Elimination:
In adult anaesthetized patients with normal renal function the effective half-life of sugammadex is about 2.5 hours and the estimated plasma clearance is about 75 ml/min (based on compartmental pharmacokinetic analysis, using three compartments). A mass balance study demonstrated that > 90% of the dose was excreted within 24 hours. 96% of the dose was excreted in urine, of which at least 95% could be attributed to unchanged sugammadex. Excretion via faeces or expired air was less than 0.02% of the dose. Administration of sugammadex to healthy volunteers resulted in increased renal elimination of rocuronium in complex.
Special populations:
Renal impairment and age:
In two pharmacokinetic studies comparing patients with severe renal impairment to patients with normal renal function, sugammadex levels in plasma were similar during at least the first 20 minutes after dosing, and thereafter the levels decreased faster in the control group. Total exposure to sugammadex was prolonged, leading to approximately 15-fold higher exposure in patients with severe renal impairment. In some of the patients with severe renal insufficiency, sugammadex levels were minimally detectable in plasma one month after dosing.
Predic |
