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Modeling kinetics of subcellular disposition of chemicals.

Balaz S - Chem. Rev. (2009)

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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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Concentration−lipophilicity profiles of chemicals in the last compartment of the water−bilayer−water−bilayer system (A) without elimination, (B) with elimination from either both aqueous phases, or (C) with elimination from the intracellular aqueous phase after the following distribution periods (in time units): 0.1 (green), 1 (blue), 100 (red), and ∞ (black).(2089) The elimination rate constants are identical for all compounds and set to zero, except k1 = k3 = 1/(time unit) in panel B and k3 = 1/(time unit) in panel C. Other details are as given in Figure 15 in section .
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fig22: Concentration−lipophilicity profiles of chemicals in the last compartment of the water−bilayer−water−bilayer system (A) without elimination, (B) with elimination from either both aqueous phases, or (C) with elimination from the intracellular aqueous phase after the following distribution periods (in time units): 0.1 (green), 1 (blue), 100 (red), and ∞ (black).(2089) The elimination rate constants are identical for all compounds and set to zero, except k1 = k3 = 1/(time unit) in panel B and k3 = 1/(time unit) in panel C. Other details are as given in Figure 15 in section .

Mentions: The majority of previously published studies by other authors on the description of movement of chemicals through a series of alternating aqueous phases and membranes focus exclusively on the nonequilibrium period of transport when none of the studied chemicals have achieved the partitioning equilibrium. We also simulated this period and compared the results with those obtained in the most advanced studies by Kubinyi.8,64 The results of the simulations for the nonequilibrium period were practically identical, despite different integration methods. However, the interpretation of the results and their application to experimental data were somewhat different. Kubinyi made all the coefficients in eq 9 freely adjustable, whereas, in our approach, a tighter adherence to the simulation results had been chosen. The resulting concentration−lipophilicity profiles for individual compartments are given in Figure 18. For the first two compartments, the curves exhibit the zero slope values in some linear parts. Other curves consist of linear ascending and descending parts, connected with a rounded apical part. The curves are symmetrical for the aqueous phases (odd compartment numbers) and asymmetrical for the membranes (even compartment numbers). The slopes of the linear parts (Figures 18−20 and 22A) are integers, which are characteristic of the corresponding compartments (Table 6).8,2083,2087 This fact significantly promotes elucidation of the action mechanisms of bioactive chemicals, as the shape of the relationship between bioactivity and lipophilicity under the nonequilibrium conditions could indicate the sequential number and the nature of the compartment, where the receptors for the studied bioactivity are localized.


Modeling kinetics of subcellular disposition of chemicals.

Balaz S - Chem. Rev. (2009)

Concentration−lipophilicity profiles of chemicals in the last compartment of the water−bilayer−water−bilayer system (A) without elimination, (B) with elimination from either both aqueous phases, or (C) with elimination from the intracellular aqueous phase after the following distribution periods (in time units): 0.1 (green), 1 (blue), 100 (red), and ∞ (black).(2089) The elimination rate constants are identical for all compounds and set to zero, except k1 = k3 = 1/(time unit) in panel B and k3 = 1/(time unit) in panel C. Other details are as given in Figure 15 in section .
© Copyright Policy - open-access - ccc-price
Related In: Results  -  Collection

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

fig22: Concentration−lipophilicity profiles of chemicals in the last compartment of the water−bilayer−water−bilayer system (A) without elimination, (B) with elimination from either both aqueous phases, or (C) with elimination from the intracellular aqueous phase after the following distribution periods (in time units): 0.1 (green), 1 (blue), 100 (red), and ∞ (black).(2089) The elimination rate constants are identical for all compounds and set to zero, except k1 = k3 = 1/(time unit) in panel B and k3 = 1/(time unit) in panel C. Other details are as given in Figure 15 in section .
Mentions: The majority of previously published studies by other authors on the description of movement of chemicals through a series of alternating aqueous phases and membranes focus exclusively on the nonequilibrium period of transport when none of the studied chemicals have achieved the partitioning equilibrium. We also simulated this period and compared the results with those obtained in the most advanced studies by Kubinyi.8,64 The results of the simulations for the nonequilibrium period were practically identical, despite different integration methods. However, the interpretation of the results and their application to experimental data were somewhat different. Kubinyi made all the coefficients in eq 9 freely adjustable, whereas, in our approach, a tighter adherence to the simulation results had been chosen. The resulting concentration−lipophilicity profiles for individual compartments are given in Figure 18. For the first two compartments, the curves exhibit the zero slope values in some linear parts. Other curves consist of linear ascending and descending parts, connected with a rounded apical part. The curves are symmetrical for the aqueous phases (odd compartment numbers) and asymmetrical for the membranes (even compartment numbers). The slopes of the linear parts (Figures 18−20 and 22A) are integers, which are characteristic of the corresponding compartments (Table 6).8,2083,2087 This fact significantly promotes elucidation of the action mechanisms of bioactive chemicals, as the shape of the relationship between bioactivity and lipophilicity under the nonequilibrium conditions could indicate the sequential number and the nature of the compartment, where the receptors for the studied bioactivity are localized.

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