Determination of interstitial rocuronium concentrations in the muscle tissue of anesthetized dogs by microdialysis.
BACKGROUND
The objective was to establish and validate a microdialysis technique for the quantification of interstitial concentrations of the neuromuscular blocker, rocuronium, in the muscle tissue of dogs under steady-state conditions.


METHODS
The standard and combined retrodialysis approaches were used for in vivo microdialysis probe calibration. After induction of anesthesia with pentobarbital (30 mg/kg), the left femoral vein was cannulated and blood drawn for protein binding determination. Microdialysis probes were inserted in the muscle and calibrated in vivo, using vecuronium as the calibrator. Each dog received a short 2-min infusion followed by a 120-min infusion of rocuronium via the right jugular vein and three microdialysis samples were collected at steady-state during a 2-h period. Samples were stored at -70 degrees C until HPLC analysis.


RESULTS
Using combined retrodialysis, rocuronium unbound interstitial (C(ISFu)) and venous plasma (C(pssuv)) concentrations are in good agreement; with a ratio C(ISFu)/C(pssuv) of 100+/-11%. Using standard retrodialysis, this ratio was 47+/-7%.


CONCLUSIONS
Combined retrodialysis is a more reliable and accurate technique for quantitative assessment of rocuronium interstitial concentrations especially for lengthy anesthetic procedures. These findings have potential implications, as drug concentrations in the site of action would be more relevant for concentration-effect relation of muscle relaxants.
Ezzine
Samia
S
Faculté de Pharmacie, Université de Montréal, 2900 Edouard Montpetit, CP 6128, succursale Centre-ville, Montreal, Quebec, Canada H3C 3 J7.
Yamaguchi
Nobuharu
N
Varin
France
F
D000732:Androstanols / Q000008:administration & dosage / Q000032:analysis* / Q000493:pharmacokinetics; D000758:Anesthesia; D000818:Animals; D004285:Dogs / Q000378:metabolism*; D045604:Extracellular Fluid / Q000737:chemistry* / Q000378:metabolism; D006993:Hypnotics and Sedatives / Q000008:administration & dosage; D007262:Infusions, Intravenous; D008297:Male; D017551:Microdialysis / Q000379:methods*; D018482:Muscle, Skeletal / Q000737:chemistry* / Q000378:metabolism; D003473:Neuromuscular Nondepolarizing Agents / Q000008:administration & dosage / Q000032:analysis* / Q000493:pharmacokinetics; D010424:Pentobarbital / Q000008:administration & dosage; D015203:Reproducibility of Results; D000077123:Rocuronium
D000732:Androstanols; D006993:Hypnotics and Sedatives; D003473:Neuromuscular Nondepolarizing Agents; D010424:Pentobarbital; D000077123:Rocuronium