Sugammadex is cleared rapidly and primarily unchanged via renal excretion

Abstract

Sugammadex is a modified γ‐cyclodextrin which rapidly reverses rocuronium‐and vecuronium‐induced neuromuscular blockade. Previous studies suggest that sugammadex is mostly excreted unchanged via the kidneys. This single‐center, open‐label, non‐randomized study used 14C‐labeled sugammadex to further investigate the excretion, metabolic and pharmacokinetic (PK) profiles of sugammadex in six healthy male volunteers. 14C‐labeled sugammadex 4 mg/kg (0.025 MBq/kg of 14C‐radioactivity) was administered as a single intravenous bolus. Blood, urine, feces and exhaled air samples were collected at pre‐defined intervals for assessment of sugammadex by liquid chromatography‐mass spectrometry (LC‐MS) and for radioactivity measurements. Adverse events were also assessed. Excretion of sugammadex was rapid with ∼70% of the dose excreted within 6 h and ∼90% within 24 h. Less than 0.02% of radioactivity was excreted in feces or exhaled air. Ninety‐five percent of the radioactivity detected in urine could be attributed to sugammadex, as determined by LC‐MS, suggesting very limited metabolism of sugammadex. LC‐MS analysis of plasma samples found that sugammadex accounted for 100% of total 14C‐radioactivity in the plasma. In general, PK parameters determined from radioactivity and sugammadex plasma concentrations were very similar. Any adverse events were of mild‐to‐moderate intensity, and judged unrelated to sugammadex. These findings demonstrate that sugammadex is cleared rapidly, almost exclusively via the kidney, with minimal or no metabolism. Copyright © 2011 John Wiley & Sons, Ltd.

Reversal of Rocuronium-Induced Neuromuscular Block with Sugammadex and Resulting Histopathological Effects in Rat Kidneys

“…It acts by forming irreversible complexes at 1:1 ratio with free rocuronium molecules in the blood followed by elimination of sugammadex-rocuronium complex through renal excretion without any metabolization. 1,2 The recommended dose range for sugammadex is 2-16 mg/kg in humans, 3,4 however, doses up to 96 mg/kg has been used in a human tolerance study conducted by Peeters and colleagues. 5 They showed that sugammadex alone is well tolerated in a limited subject population of 13, with only 1 subject experiencing adverse effects attributable to sugammadex hypersensitivity.…”

Sugammadex: A neuromuscular blockade agent encapsulator

“…Therefore, at this time standard dosing continues to be based on weight and train of four twitches as outlined in the Hepatic metabolism is responsible for rocuronium and vecuronium clearance; renal clearance regulates the sugammadex-NMBA complex elimination. 10,[18][19][20][21][22][23][24] In healthy kidneys with a glomerular filtration rate (GFR) of 75-120 ml/min, 70% of the dose is excreted in six hours, and 80-90% in 24 hours. 21,25,26 In renal failure, with GFR <30ml/min, only 29% of the dose administered is cleared by 72 hours.…”

“…10,[18][19][20][21][22][23][24] In healthy kidneys with a glomerular filtration rate (GFR) of 75-120 ml/min, 70% of the dose is excreted in six hours, and 80-90% in 24 hours. 21,25,26 In renal failure, with GFR <30ml/min, only 29% of the dose administered is cleared by 72 hours. 24 The use of high-flux dialysis removes the bound sugammadex, but at this time sugammadex administration is not recommended for patients with severe renal dysfunction.…”

Sugammadex

“…1,7 More than 90% of the dose is excreted within 24 hours, with 96% excreted in the urine. 1,9 Renal excretion (as unchanged drug) is the only observed route of elimination. No metabolism has been observed.…”