Intra-species extrapolation in risk assessment of different classes of antimicrobials

The risk assessment process for non-carcinogens incorporates all available scientific information, including toxicokinetic and toxicodynamic data. A 1 0-fold uncertainty factor (UF) is most commonly used to account for underly ing variability within the human species. The purposes of this investigatio n are to evaluate whether the magnitude of the 10X-UF can be reduced when p harmacokinetic and pharmacodynamic data are incorporated to characterize in terindividual variability and whether another UF is needed for the children group. An extensive literature search was conducted on seven antimicrobial s in order to incorporate information on kinetics and dynamics to allow ext rapolation among susceptible humans. The drugs are cefaclor, cefuroxime, er ythromycin, clarithromycin, ampicillin, gentamicin and amikacin. The compos ite factor was calculated using the highest ratio for appropriate parameter s and default subfactor. According to the data, we concluded that when rele vant kinetic and dynamic data are available, replacing the default factors with actual data-derived values was possible for the antimicrobials evaluat ed and that there is no need to add another UF to the children group.