Relevance of the 10X Uncertainty Factor to the Risk Assessment of Drugs Used by Children and Geriatrics

Conventional risk assessment practices utilize a tenfold uncertainty factor (UF) to extrapolate from the general human population to sensitive subgroups, such as children and geriatrics. This study evaluated whether the tenfold UF can be reduced when pharmacokinetic and pharmacodynamic data for pharmaceuticals used by children and geriatrics are incorporated into the risk assessment for human sensitivity. Composite factors (kinetics X dynamics) were calculated from data-derived values for bumetanide, furosemide, metoprolol, atenolol, naproxen, and ibuprofen. For the compounds examined, all of the composite factors were lower than 10. Furthermore, 8 of the 12 composite factors were less than 5.5. Incorporation of human kinetic and dynamic data into risk assessment can aid in reducing the uncertainties associated with sensitive subgroups and further study is encouraged.