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• W2313737574 abstract "The present study used the published data to examine the relationship between accumulation factor (predicted value) and accumulation ratio (observed value) of a compound as a ratio of tissue concentration at 24 hr after single administration to that after repeated administration in rats. The possibility of the prediction of tissue accumulation is discussed. Reports on tissue distribution have been published for 197 compounds in six journals from 1980 to 1993, and among them 55 compounds were found in this journal, Xenobiotic Metabolism and Disposition. Detailed investigation of these 55 compounds revealed that 30 compounds showed the accumulation ratios in 350 tissues of more than 3, a tentative critical value in this study. The order of probability of showing an accumulation ratio of more than 3 was: kidney, spleen, blood, liver, adrenal and skin. We tried to obtain reasonably assessed accumulation factor and using it to predict the extent of accumulation based on tissue concentration. First, the t1/2 obtained from the concentration at terminal two points was utilized to calculated the accumulation factor and compare it with the accumulation ratio. However, most of the accumulation factors were greater than the corresponding accumulation ratios and no equivalent relationship was obtained. This led us to try another method using the t1/2 β value obtained by fitting to a multi-compartment equation (two or three exponential function) of tissue concentration after single administration. In this case, a tendency similar to that found with the previous method was obtained. Also, a tendency was found, larger accumulation factors leading to greater discrepancy between the accumulation factors and ratios. When the tissues from studies on 10 compounds were separated into four classes according to the accumulation ratio of 1-3, 3-5, 5-7 and more than 7, the t1/2 β of these tissues after single administration showed means of 50.2, 65.3, 79.0 and 100.6 hr, respectively, indicating approximately proportional relationships between both values. Some examples, on the simulation of tissue concentration for repeated administration ba sed on data from a single administration, are presented." @default.
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• W2313737574 date "1996-01-01" @default.
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• W2313737574 title "Estimation of Drug Accumulation in Repeated-Dose Tissue Distribution Studies." @default.
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• W2313737574 doi "https://doi.org/10.2133/dmpk.11.147" @default.
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