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Nonfatty acid–modulated variations in drug binding due to heparin
Author(s) -
Naranjo C A,
Khouw V,
Sellers E M
Publication year - 1982
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.1982.105
Subject(s) - drug , heparin , pharmacology , chemistry , medicine , biochemistry
Changes in free fatty acids (FFAs) do not always correlate with variations in drug binding. To dissociate heparin effects on FFAs and drug binding, six healthy fasting subjects received 50 units (USP) IV heparin (Harris L932) with and without protamine (3.2 mg IV). Protamine completely suppressed heparin‐induced rises in FFAs and warfarin free fraction (Wα), but diazepam free fraction (Dα) increased (P < 0.005). In vitro, increasing concentrations of heparin added to serum increased Dα (P < 0.0005) and Wα (P < 0.005) without changing FFAs. In eight subjects given 50 units IV heparin (Harris L014), FFAs (P < 0.001) and propranolol free fraction (Pα) rose (P < 0.01), but variations in FFAs and Pα did not correlate (r = 0.18). When two different heparin lots (Harris L014 and Organon LA39) were tested in vivo, Harris L014 heparin increased FFAs (P < 0.005) and Pα (P < 0.0005), but variations in FFAs and Pα correlated poorly (r = 0.43, P < 0.05). In contrast, the Organon LA39 heparin did not change FFAs, but did increase Pα (P < 0.0005); variations in FFAs and Pα did not correlate (r = 0.22). These results indicate that heparin‐induced variations in drug binding are not exclusively related to changes in FFAs. Clinical Pharmacology and Therapeutics (1982) 31 , 746–752; doi: 10.1038/clpt.1982.105