SOLUBILITY AND DISTRIBUTION OF HALOTHANE IN HUMAN BLOOD *

Abstract
The interactions of halothane with five major constituents of human blood were studied by equilibrium dialysis. Haemoglobin, albumin, red cell membranes and triglycerides were found to contribute significantly to the solubility, and thus the transport, of halothane in whole blood. At physiological concentrations, γ-globulin had no detectable effect on the solubility of halothane. Absorption isotherms of halothane binding to haemoglobin and albumin suggest a possible positive co-operative effect, but complete saturation of the binding sites was not observed even when the aqueous phase was saturated with halothane. The number of halothane molecules bound per albumin molecule was not significantly affected by the presence of oleic acid. For red cell ghosts and triglyceride-rich micelles (chylomicrons and very low density lipoprotein), the adsorption isotherms suggested that halothane is solubilized within the hydrophobic regions. The distribution of halothane between cells and plasma calculated from the above equilibrium dialysis results was in reasonable agreement with the distribution in whale blood determined by an independent method.