PMID- 8029794
OWN - NLM
STAT- MEDLINE
DCOM- 19940808
LR  - 20141120
IS  - 0340-6245 (Print)
IS  - 0340-6245 (Linking)
VI  - 71
IP  - 3
DP  - 1994 Mar
TI  - Pharmacokinetics and pharmacodynamics of a low molecular weight heparin 
      (enoxaparin) after subcutaneous injection, comparison with unfractionated 
      heparin--a three way cross over study in human volunteers.
PG  - 305-13
AB  - We determined, in volunteers, the plasma levels of heparin above and below the 
      critical chainlength necessary for thrombin inhibition (ACLM and BCLM), from 1 to 
      24 h after subcutaneous injection of 5000 IU unfractionated heparin (UFH), 40 mg 
      enoxaparin and 1 mg/kg body weight of enoxaparin (LMWH) (n = 12 for each dose). 
      The levels were calculated from the antithrombin- and anti-Xa activities using 
      the specific activities of the materials injected. We also determined the course 
      of thrombin- and of factor Xa generation after triggering the extrinsic system in 
      the same samples. From the thrombin generation curves, we calculated the course 
      of prothrombinase activity. When the ACLM and BCLM plasma-levels are plotted 
      against the inhibition of thrombin- and factor Xa generation, it appears that: a) 
      There is a unique dose response relationship between ACLM level and the 
      inhibition of thrombin generation, independent of whether the ACLM is derived 
      from UFH or LMWH. This relationship is not significantly altered by the BCLM 
      appearing after LMWH injection. b) There is a similar unique relationship between 
      ACLM level and the inhibition of factor Xa generation, again independent of BCLM. 
      c) Inhibition of prothrombin activation hardly contributes to the overall effect 
      on thrombin formation and is again independent of the source of ACLM. d) ACLM 
      levels were significantly higher after injection of LMWH than after UFH 
      injection, even though the amounts of ACLM injected with the highest dose of LMWH 
      were smaller than those administered in the UFH injection. We conclude that the 
      only functional difference between LMWH and UFH is the much higher 
      bioavailability of the former.(ABSTRACT TRUNCATED AT 250 WORDS)
FAU - Bendetowicz, A V
AU  - Bendetowicz AV
AD  - Department of Biochemistry, University of Limburg, Maastricht, The Netherlands.
FAU - Beguin, S
AU  - Beguin S
FAU - Caplain, H
AU  - Caplain H
FAU - Hemker, H C
AU  - Hemker HC
LA  - eng
PT  - Clinical Trial
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - Germany
TA  - Thromb Haemost
JT  - Thrombosis and haemostasis
JID - 7608063
RN  - 0 (Enoxaparin)
RN  - 0 (Factor Xa Inhibitors)
RN  - 9000-94-6 (Antithrombin III)
RN  - 9005-49-6 (Heparin)
RN  - 9035-58-9 (Thromboplastin)
RN  - EC 3.4.21.5 (Thrombin)
RN  - EC 3.4.21.6 (Factor Xa)
SB  - IM
MH  - Adult
MH  - Antithrombin III/analysis
MH  - Dose-Response Relationship, Drug
MH  - Enoxaparin/administration & dosage/blood/pharmacokinetics/*pharmacology
MH  - Enzyme Activation
MH  - Factor Xa/analysis
MH  - Factor Xa Inhibitors
MH  - Heparin/administration & dosage/blood/pharmacokinetics/pharmacology
MH  - Humans
MH  - Injections, Subcutaneous
MH  - Male
MH  - Single-Blind Method
MH  - Thrombin/analysis/antagonists & inhibitors
MH  - Thromboplastin/analysis
EDAT- 1994/03/01 00:00
MHDA- 1994/03/01 00:01
CRDT- 1994/03/01 00:00
PHST- 1994/03/01 00:00 [pubmed]
PHST- 1994/03/01 00:01 [medline]
PHST- 1994/03/01 00:00 [entrez]
PST - ppublish
SO  - Thromb Haemost. 1994 Mar;71(3):305-13.