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  • Title: Influence of protamine on heparin-induced increases of lidocaine free fraction.
    Author: Dubé LM, Ho-Ngoc A, Davies RF, Beanlands DS, Mousseau N, McGilveray IJ.
    Journal: Res Commun Chem Pathol Pharmacol; 1983 Dec; 42(3):401-15. PubMed ID: 6665299.
    Abstract:
    It has been suggested that heparin-induced increases in drug free fraction are largely artifactual as a result of continued in vitro activity of lipoprotein lipases after blood samples collection. The influence of different concentrations of protamine (1.0, 2.5, 5.0 and 10.0 mg/ml), an inhibitor of lipoprotein lipases, on lidocaine free fraction was studied before (control) and 10 min after heparinization (3000 IU) in 7 cardiac catheterized patients. Heparin increased the mean free fraction of lidocaine by 85% (p less than 0.001) and was associated with more than 2-fold increases in free fatty acids (FFAs). The presence of protamine at 2.5, 5.0 and 10.0 mg/ml diminished both the heparin-induced elevation of lidocaine free fraction (p less than 0.001) and FFAs (p less than 0.001). At a protamine concentration of 10.0 mg/ml, the FFAs remained higher than control value (p less than 0.05) while the free fraction was not different from control preheparin value. There were significant relationships (p less than 0.01) between log protamine concentration and the changes in both free fraction (r2 = 0.906) and FFAs (r2 = 0.931). The inhibitor also reduced (p less than 0.01) the lidocaine free fraction in control samples but these changes were not correlated with changes of FFAs. These results indicate that it is impossible, at this point, to abolish the artifactual effect of heparin without altering protein binding of lidocaine.
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