title: Pharmacokinetics of cisatracurium in patients receiving nitrous oxide/opioid/barbiturate anesthesia.
abstract: BACKGROUND
  Cisatracurium, one of the ten isomers in atracurium, is a nondepolarizing muscle relaxant with an intermediate duration of action. It is more potent and less likely to release histamine than atracurium. As one of the isomers composing atracurium, it presumably undergoes Hofmann elimination. This study was conducted to describe the pharmacokinetics of cisatracurium and its metabolites and to determine the dose proportionality of cisatracurium after administration of 2 or 4 times the ED(95).
  
  
  METHODS
  Twenty ASA physical status 1 or 2 patients undergoing elective surgery under nitrous oxide/opioid/barbiturate anesthesia were studied. Patients received a single rapid intravenous bolus does of 0.1 or 0.2 mg x kg-1 (2 or 4 times the ED(95), respectively) cisatracurium. All patients were allowed to recover spontaneously to a train-of-four ratio > or = 0.70 after cisatracurium-induced neuromuscular block. Plasma was extracted, acidified, and stored frozen before analysis for cisatracurium, laudanosine, the monoquaternary acid, and the monoquaternary alcohol metabolite.
  
  
  RESULTS
  The clearances (5.28 +/- 1.23 vs. 4.66 +/- 0.67 ml x min(-1) x kg(-1) and terminal elimination half-lives (22.4 +/- 2.7 vs. 25.5 +/- 4.1 min) were not statistically different between patients receiving 0.1 mg x kg(-1) and 0.2 mg x kg(-1), respectively. Maximum concentration values for laudanosine averaged 38 +/- 21 and 103 +/- 34 ng x ml(-1) for patients receiving the 0.1 and 0.2 mg x kg(-1) doses, respectively. Maximum concentration values for monoquaternary alcohol averaged 101 +/- 27 and 253 +/- 51 ng x ml(-1), respectively. Monoquaternary acid was not quantified in any plasma sample.
  
  
  CONCLUSIONS
  Cisatracurium undergoes Hofmann elimination to form laudanosine. The pharmacokinetics of cisatracurium are independent of dose after single intravenous doses of 0.1 and 0.2 mg x kg(-1).
authors.affiliation: Department of Anesthesiology, The New York Hospital-Cornell Medical Center, New York 10021, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Lien
authors.forename: V D
authors.initials: VD
authors.lastname: Schmith
authors.forename: M R
authors.initials: MR
authors.lastname: Belmont
authors.forename: A
authors.initials: A
authors.lastname: Abalos
authors.forename: D F
authors.initials: DF
authors.lastname: Kisor
authors.forename: J J
authors.initials: JJ
authors.lastname: Savarese
mesh_terms: D000328:Adult; D000368:Aged; D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D001279:Atracurium / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D005283:Fentanyl; D006801:Humans; D007546:Isoquinolines / Q000493:pharmacokinetics; D008297:Male; D008874:Midazolam; D008875:Middle Aged; D003473:Neuromuscular Nondepolarizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D009609:Nitrous Oxide; D009892:Opium / Q000493:pharmacokinetics; D013237:Stereoisomerism; D013874:Thiopental
chemical_list: D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D007546:Isoquinolines; D003473:Neuromuscular Nondepolarizing Agents; D001279:Atracurium; D009892:Opium; C001522:laudanosine; D013874:Thiopental; D009609:Nitrous Oxide; D008874:Midazolam; D005283:Fentanyl