Lipid solubility of a series of drugs and its relevance to fatal poisoning.

For 11 commonly used drugs, the n-octanol/water partition coefficient (pH 7.4 temperature 37 degrees C) and solubility in n-octanol were determined. The drugs tested were chlorpromazine, amitriptyline, trazodone, dextropropoxyphene, diltiazem, dibucaine, amethocaine, procaine, quinidine, acetylsalicylic acid and paracetamol. For eight of the drugs, the relative lipid saturation corresponding to a fatal plasma concentration was estimated from the two parameters determined above and the median fatal blood concentrations reported in the literature. For five of those eight drugs, the estimated relative saturation in the lipid phase fell within the range 0.001-0.004 which is close to relative saturation figures in aqueous and vapour phases already published for chemicals possessing a non-specific or physical mechanism of toxicity. Since this is determined largely by their lipid solubility, it is probable that accumulation in the lipid phase is an important determinant of the lethal toxicity of drugs and chemicals with a non-specific mechanism of toxicity.