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Variability in heparin effect on serum drug binding
Author(s) -
Naranjo C A,
Sellers E M,
Khouw V,
Alexander P,
Fan T,
Shaw J
Publication year - 1980
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1980.201
Subject(s) - heparin , dialysis , medicine , diazepam , anticoagulant , saline , endocrinology , pharmacology
Heparinized saline was given to seven men and one woman, aged 21 to 42 yr, after a 14‐hr fasting period and 2 hr after breakfast; blood was collected in nonheparinized tubes. Diazepam (Dα) and warfarin (Wα) free fractions were determined in serum by equilibrium dialysis to which radiolabeled drug was added. After 50 U * heparin (Harris LO14) intravenously, the maximum effect on Dα, Wα, and free fatty acids (FFA) developed in 5 min and lasted 20 to 30 min. Dα rose and Wα fell (p < 0.01) at 5 min. Cumulative doses of heparin increased FFAs (F 4,16 = 18.29, p < 0.0005). Dα rises (r = 0.73, p < 0.001) and Wα falls (r = −0.74, p < 0.001) correlated with changes in FFAs. Dα rises and Wα falls were greater postprandially than in the fasted state (p < 0.01). Five subjects were randomly assigned up to 400 U intravenously of each of two different heparin lots (Harris LO14, and Organon LA39.) The FFA rises (reflecting heparin lipolytic activity, F 1,32 = 179.62, p < 0.0005), Dα rises (F 1,32 = 34.22, p < 0.0005), and the Wa falls (F 1,32 = 33.20, p < 0.0005) by heparin Harris L014 were greater than those by heparin Organon LA39. Although small doses of heparin, such as 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. Clinical Pharmacology and Therapeutics (1980) 28, 545–550; doi: 10.1038/clpt.1980.201