Modeling kinetics of subcellular disposition of chemicals.
Affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, Fargo, North Dakota 58105, USA. firstname.lastname@example.orgShow MeSH
Mentions: The experimental examples of the complete concentration−lipophilicity profiles typical for the mixed period of distribution are rather rare, because they are only observed if the tested chemicals cover a broad range of the lipophilicity scale. Nevertheless, the fragments consisting of more than two linear parts connected by curved portions were discernible in some published concave profiles. The data usually did not cover the sufficient range of lipophilicity, and only three linear parts were seen. Such profiles were observed among those for the growth inhibition of 17 fungal strains and 14 bacterial strains by n-alkylamines with 4−18 carbons.(2093) The resulting descriptions by the bilinear equation described by eq 9 and the trilinear equation described by eq 11 with i = 2 are summarized in Tables 8 and 9, respectively. The statistical indices in Table 8 deviate slightly from the published values,(27) because of the more-precise log P values(544) used in the present study. The differences in statistical indices between eqs 9 and 11 enable an assessment of the degree of trilinearity present in the experimental data. Both equations provide almost perfect fits. The data exhibit small but systematic deviations from the bilinear equation described by eq 9, as illustrated in Figure 21 for the growth inhibition of Ctenomyces mentagrophytes.(2093) The fact that this behavior occurred in 12 of the 17 fungal strains, as compared to only 1 of the 14 bacterial strains, speaks in favor of the hypothesis about the mixed period of distribution. In contrast to bacteria, fungi contain intracellular membranes, in addition to the cell membrane. Therefore, to achieve the partitioning equilibrium, the chemicals need more time in fungi than in bacteria. The mixed period of distribution has been observed in other experimental datasets.2087,2088
Affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, Fargo, North Dakota 58105, USA. email@example.com