Biochemical and pharmacologic profile of low molecular weight heparin (LU 47311, Clivarin).
1. Clivarin is a homogeneous LMWH as determined by the data obtained in molecular profiling studies. 2. The limited biochemical studies carried out indicated that this LMWH has a specific potency of 124 anti-Xa IU/mg and a weaker APTT activity of approximately 30 U/mg. 3. Assay-dependent neutralization of the in vitro effects of Clivarin was noted. Protamine preparations at equigravimetric concentrations effectively neutralized the APTT and TT effects; however, Heptest and anti-Xa effects were only partially neutralized. In contrast, heparin's effects were completely neutralized by this agent. 4. PF 4 only partially neutralized the effects of Clivarin. Assay-dependent variations were noted in this study. 5. In comparison to heparin, the hemorrhagic effects of Clivarin were much weaker. 6. Clivarin produced a dosage-dependent antithrombotic action in both the intravenous and subcutaneous studies. This agent also showed sustained activity and better bioavailability characteristics than heparin. 7. Clivarin exhibited a distinct biochemical and pharmacologic profile that may be useful in the optimization of this agent.
Jeske
W
W
Department of Pathology, Loyola University Medical Center, Maywood Illinois 60153.
Lojewski
B
B
Walenga
J M
JM
Hoppensteadt
D
D
Ahsan
A
A
Fareed
J
J
D000818:Animals; D001760:Bleeding Time; D006470:Hemorrhage / Q000139:chemically induced; D006495:Heparin, Low-Molecular-Weight / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008297:Male; D008970:Molecular Weight; D015539:Platelet Activation / Q000187:drug effects; D010978:Platelet Factor 4 / Q000494:pharmacology; D011479:Protamines / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D012016:Reference Values; D013921:Thrombocytopenia / Q000139:chemically induced / Q000188:drug therapy
D006495:Heparin, Low-Molecular-Weight; D011479:Protamines; D011480:Protease Inhibitors; D010978:Platelet Factor 4; C094240:reviparin