Pharmacokinetics of low molecular weight heparins.
Low molecular weight heparin (LMWH) fragments have recently been proposed as antithrombotic drugs. Several fractions and fragments have been studied in human healthy volunteers: Enoxaparin (Lovenox) from Pharmuka, Fraxiparin from Choay, Fragmin from Kabi, LHN1 from Novo laboratories. The pharmacokinetics of LMWH are clearly different from those of unfractionated heparin as demonstrated by a small group of studies. In our laboratory, we undertook one study with enoxaparin. After intravenous and sub-cutaneous injection the clearance half-life of the different LMW heparins is about 3 to 4 hours. It is significantly longer for LMW heparin than for unfractionated heparin. The half-life of anti-IIa activity is similar for LMW heparins and for unfractionated heparin. However, contrary to unfractionated heparin, there is, for Enoxaparin, a difference between the two activity half-life. The anti-IIa activity half-life is smaller than that of anti-Xa activity. After intravenous and sub-cutaneous injection of 30 to 40 mg of the different fragments and fractions the biodisponibility of LMWH S.C.(A.U.C.) I.V.(A.U.C.) was about 4 times higher when compared to unfractionated heparin injected at a dose of 29 mg. In a recent study with 12 volunteers, using S.C. administration of 20, 40, 60, and 80 mg of Enoxaparin, we were able to demonstrate a good linearity between the area under the curves and the injected doses. Standard heparin is mainly cleared by a cellular mechanism while LMWH is essentially cleared by a renal mechanism. Anti-Xa activities obtained by the chromogenic technique are higher than those obtained in human plasmas with a competitive binding assay and with labelled Enoxaparin in the dog and in the rat. The persistent anti-Xa activity may be mediated by some compounds released by Enoxaparin.(ABSTRACT TRUNCATED AT 250 WORDS)
Bara
L
L
Laboratoire Central d'Hématologie, Hôtel-Dieu, Paris, France.
Samama
M
M
D000328:Adult; D001777:Blood Coagulation / Q000187:drug effects; D015951:Factor Xa; D006207:Half-Life; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D011516:Prothrombin / Q000037:antagonists & inhibitors; D015842:Serine Proteinase Inhibitors
D006495:Heparin, Low-Molecular-Weight; D015842:Serine Proteinase Inhibitors; D011516:Prothrombin; C025337:Factor IIa; D015951:Factor Xa