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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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Transport kinetics in the third, aqueous compartment of a 10-compartment system (c is the concentration, the subscript “eq” denotes equilibrium, t is time), relative to lipophilicity.(2089) For compartment numbering, see Figure 14. The chemicals accumulate above the equilibrium level (c/ceq = 1) for a significant fraction of the distribution period. The data were obtained by numerical simulation of the pure transport of the compounds, which do not interact with the headgroups, in a system of alternating aqueous phases (5) and bilayers (5), with the transfer rate parameters li and lo related to the partition coefficient P according to eqs 3.(2089) The surface corresponds to eq 10 with the values of the coefficients specified in Table 5.
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fig15: Transport kinetics in the third, aqueous compartment of a 10-compartment system (c is the concentration, the subscript “eq” denotes equilibrium, t is time), relative to lipophilicity.(2089) For compartment numbering, see Figure 14. The chemicals accumulate above the equilibrium level (c/ceq = 1) for a significant fraction of the distribution period. The data were obtained by numerical simulation of the pure transport of the compounds, which do not interact with the headgroups, in a system of alternating aqueous phases (5) and bilayers (5), with the transfer rate parameters li and lo related to the partition coefficient P according to eqs 3.(2089) The surface corresponds to eq 10 with the values of the coefficients specified in Table 5.

Mentions: We examined the complete time course of the chemical transport in closed systems with identical lipid phases.2087–2089 For this purpose, the set of linear differential equations corresponding to the reduced equations described by eqs 47 (section ) was integrated numerically. The transfer rate parameters used are dependent on the partition coefficient as given by eqs 3 with the experimentally determined values(631) of the coefficients At and Bt. The results are illustrated in Figure 15, using the kinetics of the passive chemical transport in a 10-compartment system, composed of five aqueous phases, interspersed with five bilayer cores. Before the start of the simulation, the compounds are present only in the first aqueous compartment. The concentrations are plotted as a function of the reference partition coefficient (P) and the exposure time (t). The kinetics of distribution is dependent on the position and nature of the sampling compartment. In the third compartment, representing the aqueous phase immediately following the first bilayer core, the concentrations of the chemicals initially increase and later decrease to their equilibrium magnitudes, resulting, for a certain time period, in a remarkable accumulation of the chemicals above their equilibrium levels. This phenomenon was observed in the first half of the compartments (i.e., in compartments 2−5 in this case), regardless of their aqueous or lipid nature. The decline of the concentration caused by pure transport, taking the molecules to deeper compartments (no elimination was considered in this case), can be important in biosystems that contain many compartments, such as tissues, organs, and organisms (sections −, respectively). The situation in the second half of the compartments, which are more distant from the site of administration, is completely different, as illustrated by the transport kinetics in the sixth compartment, which is shown in Figure 16. The concentrations asymptotically approach the equilibrium magnitudes, and no accumulation above the equilibrium levels is observed.


Modeling kinetics of subcellular disposition of chemicals.

Balaz S - Chem. Rev. (2009)

Transport kinetics in the third, aqueous compartment of a 10-compartment system (c is the concentration, the subscript “eq” denotes equilibrium, t is time), relative to lipophilicity.(2089) For compartment numbering, see Figure 14. The chemicals accumulate above the equilibrium level (c/ceq = 1) for a significant fraction of the distribution period. The data were obtained by numerical simulation of the pure transport of the compounds, which do not interact with the headgroups, in a system of alternating aqueous phases (5) and bilayers (5), with the transfer rate parameters li and lo related to the partition coefficient P according to eqs 3.(2089) The surface corresponds to eq 10 with the values of the coefficients specified in Table 5.
© Copyright Policy - open-access - ccc-price
Related In: Results  -  Collection

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

fig15: Transport kinetics in the third, aqueous compartment of a 10-compartment system (c is the concentration, the subscript “eq” denotes equilibrium, t is time), relative to lipophilicity.(2089) For compartment numbering, see Figure 14. The chemicals accumulate above the equilibrium level (c/ceq = 1) for a significant fraction of the distribution period. The data were obtained by numerical simulation of the pure transport of the compounds, which do not interact with the headgroups, in a system of alternating aqueous phases (5) and bilayers (5), with the transfer rate parameters li and lo related to the partition coefficient P according to eqs 3.(2089) The surface corresponds to eq 10 with the values of the coefficients specified in Table 5.
Mentions: We examined the complete time course of the chemical transport in closed systems with identical lipid phases.2087–2089 For this purpose, the set of linear differential equations corresponding to the reduced equations described by eqs 47 (section ) was integrated numerically. The transfer rate parameters used are dependent on the partition coefficient as given by eqs 3 with the experimentally determined values(631) of the coefficients At and Bt. The results are illustrated in Figure 15, using the kinetics of the passive chemical transport in a 10-compartment system, composed of five aqueous phases, interspersed with five bilayer cores. Before the start of the simulation, the compounds are present only in the first aqueous compartment. The concentrations are plotted as a function of the reference partition coefficient (P) and the exposure time (t). The kinetics of distribution is dependent on the position and nature of the sampling compartment. In the third compartment, representing the aqueous phase immediately following the first bilayer core, the concentrations of the chemicals initially increase and later decrease to their equilibrium magnitudes, resulting, for a certain time period, in a remarkable accumulation of the chemicals above their equilibrium levels. This phenomenon was observed in the first half of the compartments (i.e., in compartments 2−5 in this case), regardless of their aqueous or lipid nature. The decline of the concentration caused by pure transport, taking the molecules to deeper compartments (no elimination was considered in this case), can be important in biosystems that contain many compartments, such as tissues, organs, and organisms (sections −, respectively). The situation in the second half of the compartments, which are more distant from the site of administration, is completely different, as illustrated by the transport kinetics in the sixth compartment, which is shown in Figure 16. The concentrations asymptotically approach the equilibrium magnitudes, and no accumulation above the equilibrium levels is observed.

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