title: Reduced clearance of rocuronium and sugammadex in patients with severe to end-stage renal failure: a pharmacokinetic study.
abstract: BACKGROUND
  Sugammadex is a selective relaxant binding agent designed to encapsulate the neuromuscular blocking agent, rocuronium. The sugammadex-rocuronium complex is eliminated by the kidneys. This trial investigated the pharmacokinetics (PKs) of sugammadex and rocuronium in patients with renal failure and healthy controls.
  
  
  METHODS
  Fifteen ASA class II-III renal patients [creatinine clearance (CL(CR)) <30 ml min(-1)] and 15 ASA I-II controls (CL(CR) > or =80 ml min(-1)) were included. After induction of anaesthesia, a single i.v. dose of rocuronium 0.6 mg kg(-1) was given, followed by a single i.v. dose of sugammadex 2.0 mg kg(-1) at reappearance of the second twitch of the train-of-four response. Plasma concentrations of rocuronium and sugammadex were estimated and PK variables determined using non-compartmental analyses. Percentages of sugammadex and rocuronium excreted in the urine were measured.
  
  
  RESULTS
  PK data were obtained from 26 patients. Mean total plasma clearance (CL) of sugammadex was 5.5 ml min(-1) in renal patients and 95.2 ml min(-1) in controls (P<0.05). Rocuronium CL was 41.8 ml min(-1) in renal patients and 167 ml min(-1) in controls (P<0.05). The median amount of sugammadex and rocuronium excreted in the urine over 72 h in renal patients was 29% and 4%, respectively, and 73% and 42% over 24 h in controls.
  
  
  CONCLUSIONS
  Large differences in the PKs of sugammadex and rocuronium between patients with renal failure and healthy controls were observed. The effect of renal impairment on the PK variables of rocuronium was less than with sugammadex. Urinary excretion of both drugs was reduced in renal patients.
authors.affiliation: Department of Anaesthesiology, Pain and Palliative Medicine, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands. l.staals@anes.umcn.nl
authors.forename: L M
authors.initials: LM
authors.lastname: Staals
authors.forename: M M J
authors.initials: MM
authors.lastname: Snoeck
authors.forename: J J
authors.initials: JJ
authors.lastname: Driessen
authors.forename: H W
authors.initials: HW
authors.lastname: van Hamersvelt
authors.forename: E A
authors.initials: EA
authors.lastname: Flockton
authors.forename: M W
authors.initials: MW
authors.lastname: van den Heuvel
authors.forename: J M
authors.initials: JM
authors.lastname: Hunter
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000732:Androstanols / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D000768:Anesthesia, General; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000378:metabolism* / Q000628:therapy / Q000652:urine; D008875:Middle Aged; D003473:Neuromuscular Nondepolarizing Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D006435:Renal Dialysis; D000077123:Rocuronium; D000077122:Sugammadex; D047408:gamma-Cyclodextrins / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine
chemical_list: D000732:Androstanols; D003473:Neuromuscular Nondepolarizing Agents; D047408:gamma-Cyclodextrins; D000077122:Sugammadex; D000077123:Rocuronium