Relationship between Physicochemical Properties of Medical Supplies and Serious Adverse Drug Reactions Listed in the Package Inserts.

We sought to clarify the relationship between the physicochemical properties of each medical supply and serious adverse drug reactions listed in the package inserts, by reviewing new information. We investigated 1) 1078 medicines currently available on the domestic Japanese market by using physicochemical data, such as cLogD, molecular weight (MW), and pKa and 2) the serious adverse drug reactions stated in the package inserts and the presence or absence of serious renal and liver disorders, as well as mental, extrapyramidal, and skin disorders. The renal disorders data showed: cLogD<0, adjusted odds ratio (aOR)=2.00; MW values ≥500, aOR=2.28; and pKa<7.4, aOR=1.95-2.06. The liver disorders data showed: pKa<8.4, aOR=1.83-1.95, and MW values ≥300, aOR=1.47-1.87. The mental disorders data showed: cLogD≥0, aOR=2.12, and MW values<400, aOR=2.46-2.85. The extrapyramidal disorders data showed: pKa≥6.4, aOR=4.50-11.32; cLogD≥0, aOR=4.71; and MW values<500, aOR=7.95-15.08. The skin disorders data showed: cLogD<0, aOR=1.46; MW values ≥500, aOR=1.69; and pKa<6.4, aOR=1.65 or<7.4-8.4, aOR=1.59. This information will be useful for investigating the relationships between new drugs entering the market and their potential future adverse drug reactions, and for establishing both precautionary and medical observational standards.