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 subgrou ps, such as children and geriatrics. This study evaluated whether the tenfo ld UF can be reduced when pharmacokinetic and pharmacodynamic data for phar maceuticals used by children and geriatrics are incorporated into the risk assessment for human sensitivity. Composite factors (kinetics x dynamics) w ere calculated from data-derived values for bumetanide, furosemide, metopro lol, atenolol, naproxen, and ibuprofen. For the compounds examined, all of the composite factors were lower than 10. Furthermore, 8 of the 12 composit e factors were less than 5.5. Incorporation of human kinetic and dynamic da ta into risk assessment can aid in reducing the uncertainties associated wi th sensitive subgroups and further study is encouraged.