British Journal of Anaesthesia, 1976, Vol. 48, No. 4 279-296
© 1976 The Board of Management and Trustees of the British Journal of Anaesthesia
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PHARMACOKINETICS OF HALOTHANE IN THE DOG
Department of Anaesthetics, Welsh National School of Medicine, Cardiff CF4 4XN.
After surgical preparation under pentobarbitone anaesthesia seven dogs of mean body weight 31 kg were ventilated with 1 % halothane for 80 min. At 1, 2, 5, 10, 20, 40 and 80 min after the start of the halothane administration blood samples were taken from the femoral artery and pulmonary artery and from a cerebral, a renal and a femoral vein. At 80 min a biopsy sample of skeletal muscle (psoas) was taken. The halothane tension in all samples was determined by extraction into carbon tetrachloride followed by gas chromatographic analysis using chloroform as an internal standard. The measured tensions were compared with tensions computed from a multi-compartment model of the uptake and distribution of halothane in the body. The model was quantified by measurements, in each individual, of total body mass, the masses of the major organs and the solubility of halothane in the major organs and tissues; by measurements of blood volume and solubility in blood at the start and finish of the halothane administration and by repeated measurements of alveolar ventilation, cardiac output and body temperature. For the original version of the model, the computed tensions deviated from the measured tensions to an extent greater than could be attributed to experimental error and in a manner which could be attributed to metabolism of halothane and probably to direct diffusion of halothane from well-perfused organs and lean tissues into fat. Direct experimental evidence of diffusion into perirenal fat was obtained in supplementary experiments. With the quantitation of the model distorted to mimic the processes of metabolism and diffusion, measured arterial tensions could be predicted with a mean error of — 0.2 mm Hg (SD 0.6 mm Hg). The mean measured arterial tension was 3.5 mm Hg.
*Computer Unit, University of Essex, Wivenhoe Park, Colchester, Essex CO4 3SQ.
Department of Drug Metabolism, Hoechst Pharmaceuticals Research Ltd, Walton Manor, Walton, Milton Keynes, Bucks MK7 7AJ.
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