title: Rocuronium pharmacokinetic-pharmacodynamic relationship under stable propofol or isoflurane anesthesia.
abstract: OBJECTIVE
  To compare the pharmacokinetics, pharmacodynamics and the concentration-effect relationship of rocuronium in patients under stable propofol or isoflurane anesthesia.
  
  
  METHODS
  Ten patients were randomized to receive fentanyl, propofol and nitrous oxide (60%) or fentanyl, thiopental, isoflurane (1.2% end-tidal concentration) and nitrous oxide (60%). To obtain good intubation conditions and maintain adequate muscle relaxation during surgery, patients received two bolus doses of rocuronium: 0.5 mg x kg(-1) (1.7 x ED95) at induction followed one hour later by 0.3 mg x kg(-1) (1 x ED95). Arterial blood samples were obtained over six hours after the second bolus dose. Plasma concentrations of rocuronium were measured using high pressure liquid chromatography. Muscle twitch tension was monitored by mechanomyography for the two doses. Pharmacokinetic and pharmacodynamic parameters were determined.
  
  
  RESULTS
  No differences in rocuronium pharmacokinetic parameters were observed between both groups. After the second bolus, clinical duration was 20 +/- 6 min in the propofol group vs 39 +/- 8 min in the isoflurane group (P <0.05). The effect compartment concentration corresponding to 50% block, EC50, was higher under propofol anesthesia: 1008 vs 592 microg x L(-1) (P <0.05).
  
  
  CONCLUSIONS
  Rocuronium body disposition is similar under stable propofol or isoflurane anesthesia. In contrast to isoflurane, propofol does not prolong the neuromuscular block. Therefore, the potentiating effect of isoflurane is of pharmacodynamic origin only, as explained by an increased sensitivity at the neuromuscular junction. In contrast with isoflurane anesthesia where the dose of rocuronium has to be decreased under stable conditions, no dose adjustment is required under propofol anesthesia.
authors.affiliation: De la Faculté de pharmacie, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Alexandrina
authors.initials: A
authors.lastname: Dragne
authors.forename: France
authors.initials: F
authors.lastname: Varin
authors.forename: Benoît
authors.initials: B
authors.lastname: Plaud
authors.forename: François
authors.initials: F
authors.lastname: Donati
mesh_terms: D000328:Adult; D000368:Aged; D000732:Androstanols / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000758:Anesthesia; D000768:Anesthesia, General; D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007530:Isoflurane; D008297:Male; D008365:Manometry; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D003473:Neuromuscular Nondepolarizing Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D015742:Propofol; D000077123:Rocuronium; D014018:Tissue Distribution
chemical_list: D000732:Androstanols; D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D003473:Neuromuscular Nondepolarizing Agents; D007530:Isoflurane; D000077123:Rocuronium; D015742:Propofol