Sugammadex is Cleared Rapidly and Primarily Unchanged via Renal Excretion

Pierre Peeters (1) , Paul Passier (2, 3) , Jean Smeets (2, 4) , Alex Zwiers (2) , Marcel de Zwart (2) , Saskia van de Wetering-Krebbers (2) , Marlou van Iersel (2) , Sjoerd van Marle (5) , Diels van den Dobbelsteen (2)

1 Early Stage Development
2 MSD
3 Astellas
4 LAP&P Consultants BV
5 PRA International

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.

Mots clés: Life Sciences

Pierre Peeters, Paul Passier, Jean Smeets, Alex Zwiers, Marcel de Zwart, et al.. Sugammadex is Cleared Rapidly and Primarily Unchanged via Renal Excretion. Biopharmaceutics & Drug Disposition, 2011, 32 (3), pp.159. ⟨10.1002/bdd.747⟩. ⟨hal-00618170⟩