PHARMACOKINETICS OF HALOTHANE IN THE DOG

After surgical preparation under pentobarbitone anaesthesiaseven 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 afterthe start of the halothane administration blood samples weretaken from the femoral artery and pulmonary artery and froma cerebral, a renal and a femoral vein. At 80 min a biopsy sampleof skeletal muscle (psoas) was taken. The halothane tensionin all samples was determined by extraction into carbon tetrachloridefollowed by gas chromatographic analysis using chloroform asan internal standard. The measured tensions were compared withtensions computed from a multi-compartment model of the uptakeand distribution of halothane in the body. The model was quantifiedby measurements, in each individual, of total body mass, themasses of the major organs and the solubility of halothane inthe major organs and tissues; by measurements of blood volumeand solubility in blood at the start and finish of the halothaneadministration and by repeated measurements of alveolar ventilation,cardiac output and body temperature. For the original versionof the model, the computed tensions deviated from the measuredtensions to an extent greater than could be attributed to experimentalerror and in a manner which could be attributed to metabolismof halothane and probably to direct diffusion of halothane fromwell-perfused organs and lean tissues into fat. Direct experimentalevidence of diffusion into perirenal fat was obtained in supplementaryexperiments. With the quantitation of the model distorted tomimic the processes of metabolism and diffusion, measured arterialtensions could be predicted with a mean error of — 0.2mm Hg (SD 0.6 mm Hg). The mean measured arterial tension was3.5 mm Hg. ^*Computer Unit, University of Essex, Wivenhoe Park, Colchester,Essex CO4 3SQ.Department of Drug Metabolism, Hoechst Pharmaceuticals ResearchLtd, Walton Manor, Walton, Milton Keynes, Bucks MK7 7AJ.