Effect of in vivo Elevation of Free Fatty Acids on Protein Binding of Drugs

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Abstract
Warfarin and diphenylhydantoin (DPH) were displaced from plasma proteins in rats by in vivo elevation of free fatty acids (FFA) produced by exercise or by i.p. injection of d,l-epinephrine (2 mg/kg). In controls FFA were 540 ± 34 μEq/l, binding of warfarin was 97.4 ± 0.2 %, that of DPH was 86.2 ± 0.4 %. Displacement of warfarin occurred consistently when FFA were higher than 750 μEq/l. In this range the concentration of unbound warfarin and the FFA level were related with a correlation coefficient of 0.79 (p < 0.05). The fraction of unbound warfarin increased up to sixfold as FFA showed concentrations of 1,600 μEq/l. Similarly, unbound DPH increased from 14 to 28 %, the corresponding correlation coefficient being 0.87 (p < 0.05).

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