title: Time course of neuromuscular effects and pharmacokinetics of rocuronium bromide (Org 9426) during isoflurane anaesthesia in patients with and without renal failure.
abstract: We have studied the onset and duration of action and pharmacokinetics of rocuronium bromide (Org 9426) during anaesthesia with nitrous oxide, fentanyl and isoflurane after a single bolus dose of rocuronium 0.6 mg kg-1 in nine patients with chronic renal failure requiring regular haemodialysis, and in nine healthy control patients. Blood samples were collected over 390 min and concentrations of rocuronium and its putative metabolites measured using HPLC. Onset time for maximum block, duration of clinical relaxation (T1(25)) and recovery index, were 61 (SD 25.0) s and 65 (16.4) s, 55 (26.9) min and 42 (9.3) min and 28 (12.3) min and 19 (8.8) min, respectively, for patients with and without renal failure. The time for TOF ratio to return spontaneously to 0.7 was 99 (41.1) min and 73 (24.2) min, respectively, in the two groups. None of these differences was significant. The pharmacokinetic data were best described by a three-exponential equation. There were significant differences between patients with and without renal failure in the rates of clearance (2.5 (1.1) ml kg-1 min-1 and 3.7 (1.4) ml kg-1 min-1, respectively) and the mean residence times (97.1 (48.7) min and 58.3 (9.6) min) P < 0.05). The differences in other kinetic parameters were not significant. We conclude that the effects of rocuronium may be prolonged in patients with renal disease, because of a decreased clearance of the drug.
authors.affiliation: Department of Anaesthetics, Queen's University of Belfast.
authors.forename: R A
authors.initials: RA
authors.lastname: Cooper
authors.forename: V R
authors.initials: VR
authors.lastname: Maddineni
authors.forename: R K
authors.initials: RK
authors.lastname: Mirakhur
authors.forename: J M
authors.initials: JM
authors.lastname: Wierda
authors.forename: M
authors.initials: M
authors.lastname: Brady
authors.forename: K T
authors.initials: KT
authors.lastname: Fitzpatrick
mesh_terms: D000328:Adult; D000732:Androstanols / Q000493:pharmacokinetics / Q000494:pharmacology*; D000769:Anesthesia, Inhalation; D005260:Female; D006801:Humans; D007530:Isoflurane; D007676:Kidney Failure, Chronic / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009469:Neuromuscular Junction / Q000187:drug effects*; D003473:Neuromuscular Nondepolarizing Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D000077123:Rocuronium; D013997:Time Factors
chemical_list: D000732:Androstanols; D003473:Neuromuscular Nondepolarizing Agents; D007530:Isoflurane; D000077123:Rocuronium