Drug Interactions at Plasma and Tissue Binding Sites

Free drug fraction vs. free drug concentration: a matter of frequent confusion

“…As noted by others, drug binding displacement has been overestimated and overstated (Rolan, 1994; McEInay, 1996) and in the veterinary literature, there are many more articles with erroneous interpretations of drug binding than articles demonstrating an actual drug–drug interaction arising from an alteration of drug binding. Such erroneous interpretations may be avoided by recalling that in vivo the effects of modifications of fu on drug plasma concentrations are exerted only through modifications of total and/or free drug clearances.…”

“…Several drugs can compete for the same plasma protein binding sites, leading potentially to drug displacements. Probably the best known example of such displacement is between warfarin and phenylbutazone (Aarons, 1981; McEInay, 1996). The competition for the same binding sites between a first drug of lower affinity termed the displaced (e.g.…”