Comparative human pharmacology of low molecular weight heparins.
The pharmacodynamics of LMW heparins differ consistently from those of normal heparin. The relative bioavailability is greater than 90% and for some LMW heparins more than 100% after subcutaneous administration, as measured by the anti-Factor Xa activity. This indicates release of endothelial bound glycosaminoglycans with anti-Factor Xa-like activities. Direct determination of the LPL and HTGL activities demonstrate higher capacities of two and a lower capacity of three LMW heparins to release these enzymes from their endothelial glycoprotein receptors into the bloodstream. Thus, all LMW heparins are characterized by improved pharmacodynamics compared with normal heparin, but their anti-Xa to APTT and anti-Xa to anti-IIa ratios and half-lives differ among each other. The neutralization of the anticoagulant effects of LMW heparins by protamine are similar in vitro and in vivo at equigravimetric doses. However, unfractionated heparin and LMW heparins are not completely antagonized by protamine on a whole blood clotting test (thrombelastography). This inhibition of Factor Xa of LMW heparins is counteracted not completely by protamine. This may be due to a release of other glucosaminoglycans by LMW heparins. The present overview demonstrates that a comparative human pharmacology gives useful devices for prophylactic and therapeutic regimen for LMW heparins in patients in addition to the data obtained from animal models.
Harenberg
J
J
First Medical Clinic, Klinikum Mannheim, University of Heidelberg, FRG.
Stehle
G
G
Augustin
J
J
Zimmermann
R
R
D000818:Animals; D001682:Biological Availability; D001780:Blood Coagulation Tests; D065427:Factor Xa Inhibitors; D006207:Half-Life; D006493:Heparin / Q000302:isolation & purification / Q000494:pharmacology; D006495:Heparin, Low-Molecular-Weight / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D007413:Intestinal Mucosa / Q000032:analysis; D011479:Protamines / Q000494:pharmacology; D011516:Prothrombin / Q000037:antagonists & inhibitors; D013552:Swine
D065427:Factor Xa Inhibitors; D006495:Heparin, Low-Molecular-Weight; D011479:Protamines; D011516:Prothrombin; C025337:Factor IIa; D006493:Heparin