Drug interactions plasma protein binding

Table 1.7.2 Interactions caused by displacement of drugs from plasma protein binding sites.

Drug Interactions During Distribution Displacement from Plasma Protein Binding Sites... 

Plasma contains a large variety of proteins, all of which have the potential to interact with drugs. Albumin is generally considered to be the most important contributor to the plasma protein binding of drugs (GIO, Gil, M16), but for some, e.g., steroids, other proteins play a major role. 

Impact of Plasma Protein Binding on PK, Exposure, Safety Margins, Potency Screens and Drug-Drug Interaction... 

Christensen, H., Baker, M., Tucker, G.T. and Rostami-Hodjegan, A. (2006) Prediction of plasma protein binding displacement and its implications for quantitative assessment of metabolic drug-drug interactions from in vitro data. Journal of Pharmaceutical Sciences, 95, 2778-2787. 

Many drugs interact with folate to affect its absorption, antagonize its biochemical activity, or increase its loss from the body. These drugs include ethanol, phenytoin, and oral contraceptives. Salicylates can compete with foUc acid for plasma protein binding. Methotrexate, a cytotoxic agent, is a folate antagonist that inhibits the biosynthesis of this coenzyme. 

Oral bioavailability is unaffected by food. Plasma protein-binding is low (3%) and distribution wide. The serum half-life is approximately 15 hours and excretion is renal. There are no known metabolites and no known interactions with the CYP450 system or other drugs. 

The mechanisms by which drug interactions alter drug distribution include (1) competition for plasma protein binding,... 

This is known as Michaelis-Menten or saturation kinetics. The processes that involve specific interactions between chemicals and proteins such as plasma protein binding, active excretion from the kidney or liver via transporters, and metabolism catalyzed by enzymes can be saturated. This is because there are a specific number of binding sites that can be fully occupied at higher doses. In some cases, cofactors are required, and their concentration may be limiting (see chap. 7 for salicylate, paracetamol toxicity). These all lead to an increase in the free concentration of the chemical. Some drugs, such as phenytoin, exhibit saturation of metabolism and therefore nonlinear kinetics at therapeutic doses. Alcohol metabolism is also saturated at even normal levels of intake. Under these circumstances, the rate of... 

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