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Modeling kinetics of subcellular disposition of chemicals.

Balaz S - Chem. Rev. (2009)

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, Fargo, North Dakota 58105, USA. stefan.balaz@ndsu.edu

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Steady-state concentrations versus lipophilicity in (A) individual aqueous phases and (B) individual bilayers for the invariant elimination rate constants. The aqueous phases are represented by compartments 3−23 and membranes are represented by compartments 2−22, both with step 4 (curves 1−6, respectively; compartment numbering is as shown in Figure 14 in section ). The curves correspond to eqs 17 and 18 with c1 = 1 unit and EM = 1 (time unit)−1. The flux terms in eqs 17 and 18 are defined in eqs 46 and only contain the surface areas and the transfer rate parameters. The transfer rate parameters are expressed by eqs 3.(2115) The dotted line indicates c1 in A and c1P in B.
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fig26: Steady-state concentrations versus lipophilicity in (A) individual aqueous phases and (B) individual bilayers for the invariant elimination rate constants. The aqueous phases are represented by compartments 3−23 and membranes are represented by compartments 2−22, both with step 4 (curves 1−6, respectively; compartment numbering is as shown in Figure 14 in section ). The curves correspond to eqs 17 and 18 with c1 = 1 unit and EM = 1 (time unit)−1. The flux terms in eqs 17 and 18 are defined in eqs 46 and only contain the surface areas and the transfer rate parameters. The transfer rate parameters are expressed by eqs 3.(2115) The dotted line indicates c1 in A and c1P in B.

Mentions: If the studied biosystem, such as a tissue, consists of the cells of the same type with similar intracellular compartments, the flux terms F are practically identical for the transport from all aqueous phases (FA, odd initial subscript i) and from all bilayers (FM, even initial subscript i). For this common situation, eq 16 can be simplified to eq 17 for the aqueous phases and eq 18 for the bilayers,(2115) with the compartment numbering given in Figure 14 in section :The dependencies on the lipophilicity of the free, non-ionized steady-state concentrations, which were attained during continuous dosing, are illustrated in Figures 26 and 27. The transfer rate parameters li and lo contained in the flux terms were expressed using eqs 3 in section , so the results are valid for the chemicals, which do not accumulate in the headgroups and at the interfaces. Interestingly, no peaks are apparent in the bilogarithmic dependencies; rather, the concentrations of chemicals are, after an initial linear increase for hydrophilic chemicals, independent of lipophilicity for aqueous phases, and rise at a lower rate for membranes. The slopes of the leftmost linear parts are dependent on the compartment number (see Figure 26). The break-point log P value is affected less by the compartment number (see Figure 26) than by the magnitude of the elimination rate (Figure 27).


Modeling kinetics of subcellular disposition of chemicals.

Balaz S - Chem. Rev. (2009)

Steady-state concentrations versus lipophilicity in (A) individual aqueous phases and (B) individual bilayers for the invariant elimination rate constants. The aqueous phases are represented by compartments 3−23 and membranes are represented by compartments 2−22, both with step 4 (curves 1−6, respectively; compartment numbering is as shown in Figure 14 in section ). The curves correspond to eqs 17 and 18 with c1 = 1 unit and EM = 1 (time unit)−1. The flux terms in eqs 17 and 18 are defined in eqs 46 and only contain the surface areas and the transfer rate parameters. The transfer rate parameters are expressed by eqs 3.(2115) The dotted line indicates c1 in A and c1P in B.
© Copyright Policy - open-access - ccc-price
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2682929&req=5

fig26: Steady-state concentrations versus lipophilicity in (A) individual aqueous phases and (B) individual bilayers for the invariant elimination rate constants. The aqueous phases are represented by compartments 3−23 and membranes are represented by compartments 2−22, both with step 4 (curves 1−6, respectively; compartment numbering is as shown in Figure 14 in section ). The curves correspond to eqs 17 and 18 with c1 = 1 unit and EM = 1 (time unit)−1. The flux terms in eqs 17 and 18 are defined in eqs 46 and only contain the surface areas and the transfer rate parameters. The transfer rate parameters are expressed by eqs 3.(2115) The dotted line indicates c1 in A and c1P in B.
Mentions: If the studied biosystem, such as a tissue, consists of the cells of the same type with similar intracellular compartments, the flux terms F are practically identical for the transport from all aqueous phases (FA, odd initial subscript i) and from all bilayers (FM, even initial subscript i). For this common situation, eq 16 can be simplified to eq 17 for the aqueous phases and eq 18 for the bilayers,(2115) with the compartment numbering given in Figure 14 in section :The dependencies on the lipophilicity of the free, non-ionized steady-state concentrations, which were attained during continuous dosing, are illustrated in Figures 26 and 27. The transfer rate parameters li and lo contained in the flux terms were expressed using eqs 3 in section , so the results are valid for the chemicals, which do not accumulate in the headgroups and at the interfaces. Interestingly, no peaks are apparent in the bilogarithmic dependencies; rather, the concentrations of chemicals are, after an initial linear increase for hydrophilic chemicals, independent of lipophilicity for aqueous phases, and rise at a lower rate for membranes. The slopes of the leftmost linear parts are dependent on the compartment number (see Figure 26). The break-point log P value is affected less by the compartment number (see Figure 26) than by the magnitude of the elimination rate (Figure 27).

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, Fargo, North Dakota 58105, USA. stefan.balaz@ndsu.edu

Show MeSH