Interstitial muscle concentrations of rocuronium under steady-state conditions in anaesthetized dogs: actual versus predicted values

• Published in: British journal of anaesthesia : BJA Vol. 94; no. 1; pp. 49 - 56
• Main Authors: Ezzine, S., Varin, F.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.01.2005; Oxford University Press; Oxford Publishing Limited (England)
• Subjects: Androstanols - blood; Androstanols - pharmacokinetics; Anesthesia; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Biological and medical sciences; dog; Dogs; Extracellular Fluid - metabolism; Male; Medical sciences; Microdialysis; model, dog; Models, Biological; Muscle, Skeletal - metabolism; Neuromuscular Junction - drug effects; Neuromuscular Junction - physiology; Neuromuscular Nondepolarizing Agents - blood; Neuromuscular Nondepolarizing Agents - pharmacokinetics; pharmacokinetics; pharmacokinetics, rocuronium; pharmacology; pharmacology, rocuronium; rocuronium; pharmacokinetics, rocuronium; model, dog; pharmacology, rocuronium; rocuronium; model; Hindlimb; Body weight; Samplings; Binding protein; Anesthesia; Interstitial; Sedative; Barbiturates; Dog; rocuronium; pharmacology; Jugular vein; Fissipedia; Carnivora; Hypnotic; Steady state; Vertebrata; Mammalia; Microdialysis; General anesthetic; Biopsy; Pentobarbital; Adult animal; Pharmacokinetics; Corrections; Comparative study
• ISSN: 0007-0912; 1471-6771
• DOI: 10.1093/bja/aei005

The objective of this study was to compare rocuronium effect (Ce) and peripheral (C2) compartment concentrations predicted by pharmacokinetic–pharmacodynamic (PK-PD) modelling with those measured in plasma (Cp) and in the interstitial fluid of muscle tissue (CISF,u) by microdialysis in anaesthetized dogs. After approval by the Animal Care Committee, eight adult male dogs with a body weight ranging from 7 to 18 kg were anaesthetized with pentobarbital. Each dog received a 2-min rocuronium infusion of 0.15 mg kg−1 min−1 followed by a 118-min infusion of 60 μg kg−1 min−1 via the right jugular vein. Arteriovenous gradient across the hindlimb was measured at 40, 60, 100 and 120 min. Three microdialysis samples were collected at 40-min intervals. Once the infusion stopped, arterial samples were collected every 2 min for the first 10 min and every 20 min for the next 120 min. Neuromuscular function was monitored using train-of-four stimulation until full recovery. Dogs were then killed and a biopsy of muscle tissue was performed (Cm). At steady state, the mean CISF,u value was 1353 ng ml−1. After correction for the unbound fraction in plasma, the mean Ce,corr and C2,corr were 1681 and 1481 ng ml−1, respectively. At the terminal sampling point, Cm was 10-fold higher than Cp. Unbound concentration of rocuronium measured in the muscle interstitial fluid under steady-state conditions confirms that parametric PK-PD modelling gives reliable estimates of effect site concentrations. Rocuronium accumulates in muscle tissue, probably by non-specific protein binding in the interstitial space.