Pharmacokinetic variables of mivacurium chloride after intravenous administration in dogs

Objective-To determine pharmacokinetic variables of mivacurium chloride aft er IV administration in dogs. Animals-5 healthy Labrador Retrievers. Procedure-Anesthesia was induced with thiopental and maintained with haloth ane in oxygen. Dogs were ventilated mechanically to an end-tidal Pco(2) val ue between 35 and 40 mm Hg. Heart rate, direct blood pressure, and arterial pH were recorded throughout the experiment. Core temperature, end-tidal Pc o(2) and halothane concentration were kept constant throughout the experime nt. Paired blood samples for determination of plasma cholinesterase activit y were collected prior to administration of a bolus of mivacurium (0.05 mg/ kg of body weight), which was administered IV during a 2-second period. Art erial blood samples were obtained for determination of plasma mivacurium co ncentration 0, 1, 3, 5, 10, 30, 60, 120, 150, and 180 minutes after adminis tration of mivacurium. Blood was collected into tubes containing EDTA and 0 .25% echothiophate. Mivacurium concentration was determined, using reversed -phase highperformance liquid chromatography. Results-For the trans-trans isomer, mean +/- SEM volume of distribution was 0.18 +/- 0.024 L/kg, median half-life was 34.9 minutes (range, 26.7 to 53. 5 minutes), and clearance was 12 +/- 2 ml/min/kg. For the cis-trans isomer, values were 0.31 0.05 L/kg, 43.4 minutes (range, 31.5 to 69.3 minutes), an d 15 +/- 2 ml/min/kg, respectively. Values for the cis-cis isomer were not calculated, because it was not detectable in plasma 60 minutes after mivacu rium administration in all 5 dogs. Conclusions and Clinical Relevance-The trans trans and cis-trans isomers of mivacurium have a long half-life and slow clearance in healthy dogs anesth etized with halothane.