title: Pharmacodynamic modelling of rocuronium in adolescents with Duchenne muscular dystrophy.
abstract: OBJECTIVE
  Studies with rocuronium showed a delayed onset and prolonged recovery in patients with Duchenne muscular dystrophy (DMD). The objective of this study was to identify the pharmacokinetic and/or pharmacodynamic origin of these alterations.
  
  
  METHODS
  Twenty-five male patients (15 with DMD, 10 controls, aged 10-18 years) were studied. Patients were anaesthetized with propofol and sufentanil. Neuromuscular transmission was monitored by acceleromyography. Patients received a single intravenous dose of 0.3 mg kg(-1) rocuronium. In five patients of the DMD group, pharmacokinetic modelling was performed from arterial rocuronium concentrations. The time course of neuromuscular block was analysed with a sigmoid E(max) model including an effect compartment.
  
  
  RESULTS
  The pharmacokinetics of rocuronium in DMD patients were Vc 63 +/- 14 ml kg(-1), Cl 3.0 +/- 1.0 ml min(-1) kg(-1), half-lives 2.0 +/- 0.6, 20 +/- 10 and 129 +/- 98 min, SE. For both the DMD and the control group, the time course of neuromuscular block could be described by a sigmoid E(max) model using the estimated pharmacokinetic parameters of the DMD group. In patients with DMD, the equilibration between the central and effect compartment was significantly slower (T(1/2)ke0: 9.7 +/- 0.3 vs. 1.3 +/- 0.1 min) and the EC(50) was significantly smaller (512 +/- 20 vs. 1170 +/- 64 ng ml(-1)), whereas the ED(50) was 0.16 +/- 0.02 mg kg(-1) in both groups.
  
  
  CONCLUSIONS
  The pharmacodynamics of rocuronium were significantly altered in patients with DMD, whereas the pharmacokinetics seemed to be similar to those in healthy adults. Patients with DMD were more sensitive with respect to effect site concentration but not with respect to dose.
authors.affiliation: Department of Anaesthesiology, University of Erlangen, Erlangen, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Ihmsen
authors.forename: Vanessa
authors.initials: V
authors.lastname: Viethen
authors.forename: Juergen
authors.initials: J
authors.lastname: Forst
authors.forename: Helmut
authors.initials: H
authors.lastname: Schwilden
authors.forename: Hubert J
authors.initials: HJ
authors.lastname: Schmitt
authors.forename: Tino
authors.initials: T
authors.lastname: Muenster
mesh_terms: D000293:Adolescent; D000732:Androstanols / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002648:Child; D006262:Health; D006801:Humans; D008297:Male; D008954:Models, Biological; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy; D000077123:Rocuronium
chemical_list: D000732:Androstanols; D000077123:Rocuronium