PMID- 8707165
OWN - NLM
STAT- MEDLINE
DCOM- 19960911
LR  - 20180216
IS  - 0301-0147 (Print)
IS  - 0301-0147 (Linking)
VI  - 26 Suppl 2
DP  - 1996
TI  - Low-molecular-weight heparins: an overview of their pharmacodynamics, 
      pharmacokinetics and metabolism in humans.
PG  - 24-38
AB  - Low-molecular-weight heparins (LMWHs) comprise a group in the class of 
      antithrombotic medications, a class headed by unfractionated heparin (UFH). The 
      LMWHs, with mean molecular weights of 4.0-6.0 kD, differ in their individual 
      manufacturing processes, the distribution of their fragment molecular weights, 
      their in vitro potency (anti-Xa, antithrombin and anticoagulant activities) and, 
      consequently, in their biodynamic patterns, recommended dose regimen, and 
      efficacy/safety ratio. Their drug disposition profiles have been evaluated using 
      two significant markers of their pharmacodynamic activity, namely anti-Xa and 
      anti-IIa activities. Since they are mainly administered subcutaneously, then 
      compared to UFH, they are almost completely absorbed (F > or = 90%) and, in 
      contrast to UFH, those for which data are available in the literature exhibit 
      linear pharmacokinetics with proportionality between anti-Xa (and anti-IIa in 
      some cases) plasma concentration and dose, and stationary distribution volume and 
      clearance processes when the dosage is increased. Their distribution volume is 
      close to the blood volume, they are partially metabolized by desulphatation and 
      depolymerization, but urinary excretion of anti-Xa activity for enoxaparin, 
      dalteparin and nadroparin, all given at doses for prevention of venous 
      thrombosis, is between 5 and 10% of the injected dose. However, these LMWHs 
      differ in the extent of their non-renal clearance, resulting in different 
      apparent elimination half-life values and relative apparent bioavailability. When 
      considering certain at-risk situations, using doses for preventing 
      thromboembolism, the LMWHs do not significantly cross the placenta of pregnant 
      women and their excretion profiles are only slightly altered in severe 
      (endogenous creatinine clearance less than 15 ml/min) renal disease patients when 
      given at doses recommended for prevention of venous thromboembolism. Because of 
      the differences among LMWHs, the clinical profile of a given LMWH cannot be 
      extrapolated to another one or generalized to the whole LMWH family.
FAU - Frydman, A
AU  - Frydman A
AD  - Rhone-Poulenc Rorer SA, Recherche et Developpement, Antony, France.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - Switzerland
TA  - Haemostasis
JT  - Haemostasis
JID - 0371574
RN  - 0 (Fibrinolytic Agents)
RN  - 0 (Heparin, Low-Molecular-Weight)
SB  - IM
MH  - Aged
MH  - Animals
MH  - Biological Availability
MH  - Biotransformation
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Fibrinolytic Agents/metabolism/pharmacokinetics/*pharmacology
MH  - Heparin, Low-Molecular-Weight/metabolism/pharmacokinetics/*pharmacology
MH  - Humans
MH  - Injections, Subcutaneous
MH  - Intestinal Absorption
MH  - Pregnancy
MH  - Tissue Distribution
RF  - 77
EDAT- 1996/01/01 00:00
MHDA- 1996/01/01 00:01
CRDT- 1996/01/01 00:00
PHST- 1996/01/01 00:00 [pubmed]
PHST- 1996/01/01 00:01 [medline]
PHST- 1996/01/01 00:00 [entrez]
AID - 10.1159/000217270 [doi]
PST - ppublish
SO  - Haemostasis. 1996;26 Suppl 2:24-38. doi: 10.1159/000217270.