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Int J Clin Pharmacol Ther. 2017 Sep;55(9):746-752. doi: 10.5414/CP203025.

Pharmacokinetics of sugammadex in subjects with moderate and severe renal impairment
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Abstract

AIMS:

Sugammadex rapidly reverses moderate and deep rocuronium- or vecuronium-induced neuromuscular blockade at doses of 4 mg/kg and 2 mg/kg, respectively. Sugammadex is renally eliminated. This study evaluated the pharmacokinetics of sugammadex in subjects with renal impairment versus those with normal renal function.

METHODS:

This open-label, two-part, phase 1 study included adults with moderate (creatinine clearance (CL<sub>cr</sub>) 30 - < 50 mL/min) and severe (CL<sub>cr</sub> < 30 mL/min) renal impairment and healthy controls (CL<sub>cr</sub> ≥ 80 mL/min). A single intravenous (IV) bolus injection of sugammadex 4 mg/kg was administered into a peripheral vein over 10 seconds directly by straight needle in part 1 (n = 24; 8/group), and via an IV catheter followed by a saline flush in part 2 (n = 18; 6/group). Plasma concentrations of sugammadex were collected after drug administration. Due to dosing issues in part 1, pharmacokinetic parameters were determined for part 2 only. Safety was assessed throughout the study.

RESULTS:

Pharmacokinetic data were obtained from 18 subjects. Mean sugammadex exposure (AUC<sub>0-∞</sub>) in subjects with moderate and severe renal impairment was 2.42- and 5.42-times, respectively, that of healthy controls. Clearance decreased and apparent terminal half-life was prolonged with increasing renal dysfunction. Similar C<sub>max</sub> values were observed in subjects with renal impairment and healthy controls. There were no serious adverse events.

CONCLUSIONS:

Sugammadex exposure is increased in subjects with moderate and severe renal insufficiency due to progressively decreased clearance as a function of worsening renal function. Sugammadex 4 mg/kg was well tolerated in subjects with renal impairment, with a safety profile similar to that of healthy subjects. These results indicate that dose adjustment of sugammadex is not required in patients with moderate renal impairment; however, current safety experience is insufficient to support the use of sugammadex in patients with CL<sub>cr</sub> < 30 mL/min.
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PMID:
28679468
DOI:
10.5414/CP203025
[Indexed for MEDLINE]

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