Drug interactions tissue binding

Clearly, the mechanistic contributors to the extent of plasma and tissue binding are numerous, and the VD term represents a simplistic picture of potentially hundreds, maybe thousands, of individual tissue binding interactions. Despite this possible complexity, there may be a few individual types of tissue binding that are mostly responsible for tissue partitioning, and as described elsewhere in this chapter, this phenomena may be more related to non-specific interactions that are a function of gross physicochemical properties of the drug than specific binding interactions. 

Chapter 15, this leads to interactions between compounds that compete for the same binding sites on serum albumin. However, coadministered compounds also may compete for tissue binding sites, as demonstrated by the interaction between quinidine and digoxin (11). The extent of drug distribution across a membrane will depend on the relative affinity of competing compounds for both plasma and tissue binding sites. 

The extent and degree of interactions between chiral macromolecules of the body and stereoisomers is a source of observable differences in isomeric drug distribution. Stereoselectivity in drug distribution may occur when tissue or protein binding or uptake is associated with structurally specific receptor, protein, or enzyme binding. Since only unbound or free drug is susceptible to elimination and distribution to receptors and other tissues and fluids, differences in the protein and tissue binding of stereoisomers are reflected in their overall pharmacokinetic profiles. 

Identical chemical and physical properties of enantiomers represent a potential source for enantiomer-enantiomer interactions at both pharmacokinetic and pharmacodynamic levels. Whether by competition for plasma- or tissue-binding sites or for drug-metabolizing enzymes, enantiomers may exhibit changes in pharmacokinetics when administered as a racemate compared to individual stereoisomers. The enantiomers of disopyramide exhibit similar clearance and volumes of distribution when given separately. " However, when administered as the racemate, the 5... 

Binding implies distribution Tissue penetration often good PK drug interactions possible PD drug interactions rare... 

Binding implies clearance Usually poor tissue penetration PK drug interactions rare PD drug interactions possible... 

Drug interactions hyperkalemia enhances effects and vice versa displaces digoxin from tissue binding sites, enhancing toxicity may oppose effects of AChE inhibitors in myasthenia. 

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