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Heparin kinetics: Variables related to disposition and dosage
Author(s) -
Cipolle Robert J,
Seifert Randall D,
Neilan Barbara A,
Zaske Darwin E,
Haus Erhardt
Publication year - 1981
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.1981.53
Subject(s) - heparin , partial thromboplastin time , volume of distribution , bolus (digestion) , medicine , therapeutic index , anticoagulant , dosing , intravenous bolus , pharmacokinetics , pharmacology , drug , anesthesia , coagulation
A method to determine heparin kinetics and dosage requirements was examined in 20 patients with active thromboembolic disease. Pretreatment heparin sensitivities were determined to establish the relationship between heparin concentration and activated partial thromboplastin times (APTTs). After an initial bolus dose, serial APTTs were measured, heparin concentrations were estimated, and kinetic determinations followed. Heparin elimination rate, distribution volume, and clearance were used to calculate dosage requirements. There was a 500% range in pretreatment heparin sensitivities. Smokers had more rapid heparin elimination rates and t½s than nonsmokers did. Men had more rapid drug clearances than women did. Body weight was related to heparin dosage requirements. Patients treated early after onset of symptoms required higher doses than patients in whom treatment was delayed. A multiple regression model was developed for heparin dosage requirements from body weight, sex, delay between onset of symptoms and treatment, and smoking. This statistical model explained 78% of the variance in heparin requirements. Clinical Pharmacology and Therapeutics (1981) 29, 387–393; doi: 10.1038/clpt.1981.53