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Sugammadex is cleared rapidly and primarily unchanged via renal excretion
Author(s) -
Peeters Pierre,
Passier Paul,
Smeets Jean,
Zwiers Alex,
de Zwart Marcel,
van de WeteringKrebbers Saskia,
van Iersel Marlou,
van Marle Sjoerd,
van den Dobbelsteen Diels
Publication year - 2011
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.747
Subject(s) - sugammadex , urine , rocuronium , pharmacokinetics , chemistry , excretion , clearance , pharmacology , anesthesia , medicine , urology , biochemistry , propofol
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 14 C‐labeled sugammadex to further investigate the excretion, metabolic and pharmacokinetic (PK) profiles of sugammadex in six healthy male volunteers. 14 C‐labeled sugammadex 4 mg/kg (0.025 MBq/kg of 14 C‐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 14 C‐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.