title: Pharmacokinetics and pharmacodynamics of rocuronium in young adult and elderly patients undergoing elective surgery.
abstract: OBJECTIVE
  To evaluate the impact of advanced age on rocuronium kinetic disposition in ASA I-III patients undergoing elective surgeries.
  
  
  METHODS
  Young adult (20-50 years, n = 15) and elderly patients (65-85 years, n = 14) submitted to surgery under general anaesthesia were investigated. All patients were induced with individual intravenous doses of midazolam, rocuronium, fentanyl and propofol. Rocuronium-induced neuromuscular block was monitored by train of four stimulations of the adductor muscle of the thumb on the ulnar nerve. The pharmacokinetic parameters were calculated by non-compartmental analysis. The relationship between rocuronium plasma concentration and the neuromuscular blockade was described by a sigmoidal Emax model.
  
  
  RESULTS
  Elderly patients presented decreased Cl (2.1 ml/kg per min vs 2.8 ml/kg per min; P = 0.0123); increased AUC/dose (507.8 μg min/ml (mg/kg) vs 392.2 μg min/ml/(mg/kg); P = 0.0168) and reduced volume of distribution (285.4 ml/kg vs 435.6 ml/kg, P = 0.0434) compared to young adults. The concentrations required to achieve 50% of maximum neuromuscular block (EC50) were similar for young adult (338.8 ng/ml) and elderly (462.7 ng/ml) patients (P > 0.05).
  
  
  CONCLUSIONS
  Elderly patients showed increased AUC/D and reduced total Cl compared to young adult patients due to the age-related reduced renal function. Differences in the PK-PD properties of rocuronium in elderly population are due to changes in drug disposition rather than to alterations in the sensitivity to the drug.
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, USP - Univ. de São Paulo, Ribeirão Preto, Brazil.
authors.forename: Renan M
authors.initials: RM
authors.lastname: Varrique
authors.affiliation: Faculdade de Medicina de Ribeirão Preto, USP - Univ. de São Paulo, Ribeirão Preto, Brazil.
authors.forename: Gabriela R
authors.initials: GR
authors.lastname: Lauretti
authors.affiliation: Faculdade de Ciências Farmacêuticas, UNESP - Univ. Estadual Paulista, Araraquara, Brazil.
authors.forename: Julia A
authors.initials: JA
authors.lastname: Matsumoto
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, USP - Univ. de São Paulo, Ribeirão Preto, Brazil.
authors.forename: Vera L
authors.initials: VL
authors.lastname: Lanchote
authors.affiliation: Faculdade de Ciências Farmacêuticas, UNESP - Univ. Estadual Paulista, Araraquara, Brazil. nmoraes@fcfar.unesp.br.
authors.forename: Natalia V
authors.initials: NV
authors.lastname: de Moraes
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000732:Androstanols / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000768:Anesthesia, General; D019540:Area Under Curve; D017558:Elective Surgical Procedures; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D061886:Neuromuscular Monitoring; D003473:Neuromuscular Nondepolarizing Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000077123:Rocuronium; D055815:Young Adult
chemical_list: D000732:Androstanols; D003473:Neuromuscular Nondepolarizing Agents; D000077123:Rocuronium
keywords: creatinine clearance; elderly; rocuronium