Pharmacokinetic variables of mivacurium chloride after intravenous administration in dogs

Abstract

Abstract Objective To determine pharmacokinetic variables of mivacurium chloride after IV administration in dogs. Animals 5 healthy Labrador Retrievers. Procedure Anesthesia was induced with thiopental and maintained with halothane in oxygen. Dogs were ventilated mechanically to an end-tidal PCO2 value between 35 and 40 mm Hg. Heart rate, direct blood pressure, and arterial pH were recorded throughout the experiment. Core temperature, end-tidal PCO2, and halothane concentration were kept constant throughout the experiment. Paired blood samples for determination of plasma cholinesterase activity 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. Arterial blood samples were obtained for determination of plasma mivacurium concentration 0, 1, 3, 5, 10, 30, 60, 120, 150, and 180 minutes after administration of mivacurium. Blood was collected into tubes containing EDTA and 0.25% echothiophate. Mivacurium concentration was determined, using reversed-phase high-performance 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), and 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 mivacurium 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 anesthetized with halothane. (Am J Vet Res 1999;60:1051-1054)