Pharmacokinetics of sugammadex in subjects with moderate and severe renal impairment

K. Chris Min, Kenneth C. Lasseter, Thomas C. Marbury, Rebecca E. Wrishko, William D. Hanley, Dennis G. Wolford, Joanna Udo de Haes, Christina Reitmann, David E. Gutstein

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

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 (CLcr) 30 – < 50 mL/min) and severe (CLcr < 30 mL/ min) renal impairment and healthy controls (CLcr ≥ 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 (AUC0–∞) 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 Cmax 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 CLcr < 30 mL/min.

Original languageEnglish
Pages (from-to)746-752
Number of pages7
JournalInternational Journal of Clinical Pharmacology and Therapeutics
Volume55
Issue number9
DOIs
StatePublished - 2017
Externally publishedYes

Keywords

  • Neuromuscular block
  • Neuromuscular block antagonism
  • Renal insufficiency
  • Rocuronium
  • Vecuronium

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