Variability in heparin effect on serum drug binding

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Abstract
Heparinized saline was given to 7 men and 1 woman, 21-42 yr old, after a 14 h fasting period and 2 h after breakfast; blood was collected in nonheparinized tubes. Diazepam (D.alpha.) and warfarin (W.alpha.) free fractions were determined in serum by equilibrium dialysis to which radiolabeled drug was added. After 50 U [USP unit] heparin (Harris LO14) i.v., the maximum effect on D.alpha., W.alpha. and free fatty acids (FFA) developed in 5 min and lasted 20-30 min. D.alpha. rose and W.alpha. fell (P < 0.01) at 5 min. Cumulative doses of heparin increased FFAs (F4,16 = 18.29, P < 0.0005). D.alpha. rises (r = 0.73, P < 0.001) and W.alpha. falls (r = -0.74, P < 0.001) correlated with changes in FFA. D.alpha. rises and W.alpha. falls were greater postprandially than in the fasted state (P < 0.01). Five subjects were randomly assigned up to 400 U i.v. of each of 2 different heparin lots (Harris LO14 and Organon LA39.) The FFA rises (reflecting heparin lipolytic activity, F1,32 = 179.62, P < 0.0005), D.alpha. rises (F1,32 = 34.22, P < 0.0005) and the W.alpha. falls F1,32 = 33.20, P < 0.0005) by heparin Harris LO14 were greater than those by heparin Organon LA39. Although small doses of heparin, e.g., those in heparin locks, can affect drug binding, the extent and variability of the effect depends on the biologic activity of the heparin and varies with manufacturer and lot, exact time of sampling and eating.