Membrane partitioning, drugs

The evaluation of the apparent ionization constants (i) can indicate in partition experiments the extent to which a charged form of the drug partitions into the octanol or liposome bilayer domains, (ii) can indicate in solubility measurements, the presence of aggregates in saturated solutions and whether the aggregates are ionized or neutral and the extent to which salts of dmgs form, and (iii) can indicate in permeability measurements, whether the aqueous boundary layer adjacent to the membrane barrier, Umits the transport of drugs across artificial phospholipid membranes [parallel artificial membrane permeation assay (PAMPA)] or across monolayers of cultured cells [Caco-2, Madin-Darby canine kidney (MDCK), etc.]. 

Avdeef, A., Box, K. J., Comer, J. E., Hibbert, C., Tam, K. Y. pH-metric logP 10. Determination of liposomal membrane-water partition coefficients of ionizable drugs. Pharm. Res. 1998,... 

To date, there have been only very few studies on the sorption of environmentally relevant HIOCs to membranes. In contrast, there exists a large body of literature on ionogenic drug partitioning (see, e.g. [3-5]), and the partitioning of hydrophobic ions [6], and the use of fluorescent membrane probes [7], This literature review attempts to relate the findings from these related scientific fields to environmental chemistry. 

Since the membrane water partition coefficient is a relevant parameter for the pharmacokinetic behaviour, i.e. drug uptake, many more studies on the speciation of drugs at membrane interphases can be found in the... 

Figure 16.1 Schematic representation of a vacuum cleaner model drug partitions into the membrane bilayer, flips across the lipid core, accesses the TMDs from the inner membrane leaflet and is released through a protein channel into the extracellular medium.

The rate of drug absorption for the transeellular route is pH dependent. Sueh dependency results from the fact that the membrane-aqueous partition coefficient for an ionizable drug is pH dependent. 

Orally administered drugs partition into the lipid bilayer in the process of diffusing across the apical and basolateral membranes of the intestinal brush border cells into the blood, as illustrated in Figure 2. About 1800 such drugs are commercially available. A small surface area of the polar parts of the drug molecule generally favors entry into the hydrophobic interior of... 

Nonspecific drug partitioning into biological membranes can be mod-... 

The interactions obviously differed between the lipid bilayers and the natural membranes. Furthermore, cholesterol slightly hinders the drug partitioning into the liquid-crystalline bilayers, in agreement with several previous reports, and the drug molecules interact electrostatically with membrane proteins at the hydrophilic interface adjacent to the polar headgroups of the phospholipid molecules (7). 

A Avdeef, KJ Box, JEA Comer, C Hibbert, KY Tam. pH-Metric log P 10. Determination of liposomal membrane-water partition coefficients of ioniz-able drugs. Pharm Res 15 209-215, 1998. 

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