Biokinetic model for the calculation of dose coefficients for oral and intravenous administration of 14C labeled drugs

A first order biokinetic model is presented for the calculation of dose coefficients from human activity excretion data after intravenous and oral administration of C-14 labeled drugs It is intended for the dose estimation in human studies in drug research, where the number of measurements is low and their uncertainty rather high. The model depends on only 6 parameters that are to be adjusted with the help of the measurement data. A comparison of measured and calculated activities in excreta of four human studies on C-14 labeled drugs revealed considerable agreement, although some limitations have to be accepted. In contrast to the biokinetic model for C-14 in organic compounds recommended by the International Commission on Radiological Protection (ICRP) the present model does not assume a fixed biological half-life of 40 days, but follows the experimental data. In consequence, the resulting dose coefficients differ from the ICRP value. For experimental data tested and assuming uniform activity distribution, the committed effective doses amount between one twenty-fifth to one fiftieth of the values calculated from the ICRP model. The uncertainty of the derived dose coefficients is estimated to be about +/- 50 %.