Interaction of phenobarbitone and ethanol in mice studied from dose‐response curves and drug concentrations in blood

The interaction of phenobarbitone and ethanol given intraperitoneally to mice has been studied. Dose‐response relations were established for incidence of death, sleeping time and time of onset of sleep. Concentrations of phenobarbitone and ethanol were assayed in whole blood samples. When the two drugs were administered together, sleep occurred more rapidly than calculated as likely on the basis of the effects of the drugs given individually. On the other hand, sleep was of shorter duration and the incidence of death was less than anticipated. These modifications of the expected effects related to drug concentration changes in blood. Isobolograms indicated the need for precision in describing the interactions as potentiation, addition or antagonism, as different terms could be applied depending on the effect measured.