The artifactual nature of heparin-induced drug protein-binding alterations

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Abstract
The purpose was to determine whether the reported alteration of protein drug binding after heparin administration in man was artifactual as result of continued in vitro activity of triglyceride lipases. The lipoprotein lipase inhibitors protamine (14 mg/ml) and EDTA (10 mg/ml) were added to blood samples from 11 healthy subjects before and 15 min after 1000 USP units of i.v. heparin. Heparin elevated total nonesterified fatty acid (NEFA) concentration (P < 0.001) and the free fractions of lidocaine, diazepam and propranolol (P < 0.001 for all). The presence of the lipase inhibitors diminished the heparin-induced elevation of NEFA (P < 0.001) and free fractions of lidocaine (P < 0.001) and diazepam (P < 0.001), but these values were still greater than control. The inhibitors reduced propranolol binding in control samples and did not diminish the effects of heparin. The change in NEFA concentrations correlated with the free fraction changes of all 3 ligands (r = 0.739-0.849). These data suggest that the heparin-induced protein binding changes are, to a large extent, in vitro artifacts.