Displacement interactions

There are two ways a solute can interact with a stationary phase surface. The solute molecule can interact with the adsorbed solvent layer and rest on the top of it. This is called sorption interaction and occurs when the molecular forces between the solute and the stationary phase are relatively weak compared with the forces between the solvent molecules and the stationary phase. The second type is where the solute molecules displace the solvent molecules from the surface and interact directly with the stationary phase itself. This is called displacement interaction and occurs when the interactive forces between the solute molecules and the stationary phase surface are much stronger than those between the solvent molecules and the stationary phase surface. An example of sorption interaction is shown in Figure 9. 

The second type of interaction, displacement interaction, is depicted in Figure 10. This type of interaction occurs when a strongly polar solute, such as an alcohol, can interact directly with the strongly polar silanol group and displaces the adsorbed solvent layer. Depending on the strength of the interaction between the solute molecules and the silica gel, it may displace the more weakly adsorbed solvent and interact directly with the silica gel but interact with the other solvent layer by sorption. Alternatively, if solute-stationary phase interactions are sufficiently strong, then the solute may displace both solvents and interact directly with the stationary phase surface. 

A. Kmmhansl, Competing displacive interactions, phonon anomalies and stmctural transitions which do... 

Solutes will interact with the reverse phase surface in much the same way as they do with the silica gel surface. There will be basically two forms of interaction, by sorption and by displacement. Sorption interaction has been experimentally confirmed by Scott and Kucera (10) by measuring the adsorption isotherm of acetophenone on the reverse phase RP18 from a 40%w/v acetonitrile mixture in water. The authors noted that there was no change in the acetonitrile concentration, as the solute was adsorbed. Displacement interactions, although certain to occur, do not appear to have been experimentally demonstrated to date. 

Vigilance for drug-drug interactions is required because of the greater number of medications prescribed to elderly patients and enhanced sensitivity to adverse effects. Pharmacokinetic interactions include metabolic enzyme induction or inhibition and protein binding displacement interactions (e.g., divalproex and warfarin). Pharmacodynamic interactions include additive sedation and cognitive toxicity, which increases risk of falls and other impairments. 

Rolan PE. Plasma protein binding displacement interactions - why are they still regarded as clinically important Br ] Clin Pharmacol 1994 37 125-8. 

DK Lloyd, S Li, P Ryan. Investigation of enantioselective ligand—protein binding and displacement interactions using capillary electrophoresis. Chirality 6 230-238, 1994. 

T Arai, N Nimura, T Kinoshita. Investigation of enantioselective ofloxacin-albumin binding and displacement interactions using capillary affinity zone electrophoresis. Biomed Chromatogr 9 68—74, 1995. 

MacKichan, J.J. (1989) Protein binding drug displacement interactions—fact or fiction Clin Pharmacokinet 16 65-73. 

MacKichan JJ. Protein binding drug displacement interactions fact or fiction Clin Pharmacokinei 1989 16 65-73. 

Rolan, P. E. Plasma Protein Binding Displacement Interactions Why Are They Still Regarded as Clinically Important Br. J. Clin. Pharm. 1994, 37, 125-128. 

Rosenthal AE (1967) A graphic method for the determination and presentation of binding parameters in a complex system. Analytical Biochemistry 20 525-532 Sansom LN, Evans AM (1995) What is the True Clinical Significance of Plasma Protein Binding Displacement Interactions Drug Safety 12(4) 227—233 Scatchard G (1949) The attractions of protein for small molecules and ions. New York Academic of Sciences 51 660-692... 

A trigonometrical calculation96 shows that an water quadrupole-ion displacement interaction energy at ionic (charge ze) distance a from the dipole center is ... 

Sansom LN, Evans AM. What is the true clinical significance of plasma protein binding displacement interactions Drug Saf 1995 12 227-33. 

For a displacement interaction to become clinically important, a second mechanism usually operates sodium valproate can cause phenytoin toxicity because it both displaces phenytoin from its binding site on plasma albumin and inhibits its metabolism. Similarly aspirin and probenecid (and possibly other nonsteroidal anti-inflammatory drugs) displace the folic acid antagonist methotrexate from its protein-binding site and reduce its rate of active secretion by the renal tubules the result is serious methotrexate toxicity. 

Finally, free drug levels may be affected by interaction with other medications, which may cause displacement of a drug off the protein. Considering that the elderly are taking more medications, they are more likely to experience protein-displacement drug interactions. However, protein-displacement interactions are not considered as clinically significant as metabolism interactions. 

Bepridil has been the subject of a brief general review (1) and its pharmacokinetics have been specifically reviewed (2). Although it is highly protein-bound, bepridil does not take part in protein-binding displacement interactions (2). 

Denson DD, Myers JA, Coyle DE. The clinical relevance of the drug displacement interaction between meperidine and bupivacaine. Res Commun Chem Pathol Pharmacol 1984 45(3) 323-30. 

The vast majority of ligands in Table V are bound in one or both sites within specialized cavities of subdomains IIA and IIIA. At this time the binding locations of several key compounds, historically used as markers in drug or ligand displacement interactions, have been determined at various resolutions (Table VI). Clearly, from Table VI it can be seen that IIIA appears to possess the primary binding activity for albumin whereas IIA is more specialized. 

I Drug Interactions. Because ethosuximide is not protein bound, displacement interactions cannot occur. The metabolism of ethosuximide may be induced by carbamazepine. A complex interaction between valproic acid and ethosuximide has been reported. Valproic acid may inhibit the metabolism of ethosuximide, but only if the metabolism of ethosuximide is near saturation. ... 

There s also a pharmacokinetic way to analyze the likely outcome of binding displacement interactions on pharmacodynamic outcomes. Steady-state unbound plasma concentrations can be defined in terms of a drug s clearance (CL), the fraction of drug absorbed (F), the dose (D), and the dosing interval, t. 

This means that overall exposure to unbound drug can t be affected by plasma binding or plasma protein binding displacement interactions. Furthermore, if the drug is a high hepatic extraction-ratio drug, such that CLint >Qj then Q hepatic blood flow rate, becomes limiting, and Equation (12.31) becomes ... 

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