PMID- 12244484
OWN - NLM
STAT- MEDLINE
DCOM- 20030711
LR  - 20141120
IS  - 0094-6176 (Print)
IS  - 0094-6176 (Linking)
VI  - 28
IP  - 4
DP  - 2002 Aug
TI  - Pharmacokinetic and pharmacodynamic characterization of a medium-molecular-weight 
      heparin in comparison with UFH and LMWH.
PG  - 369-78
AB  - Despite the well-established medical use of heparins, the question arises whether 
      the efficacy-safety ratio of the available heparins can still be improved. 
      Therefore, a medium-molecular-weight heparin (MMWH), a new heparin with an 
      average molecular weight of 10.5 kDa and a narrow molecular weight range (9.5 to 
      11.5 kDa) was developed. Its in vitro activities amount to 174.9 anti-factor Xa 
      (aXa) U/mg and 170.0 antithrombin (aIIa) U/mg. In the presented randomized, 
      double-blind, cross-over study in healthy volunteers, the pharmacokinetics and 
      pharmacodynamics of MMWH are compared with those of an unfractionated heparin 
      (UFH) and a low-molecular-weight heparin (LWMH; enoxaparin). After subcutaneous 
      administration of 9000 aXa-U of either heparin in 16 volunteers, the prolongation 
      of the activated partial thromboplastin time (aPTT), the aXa activity, and the 
      aIIa activities were determined at 11 time points spread over 24 hours after 
      injection. The ex vivo analysis revealed striking pharmacodynamic and 
      pharmacokinetic differences between the three heparins. UFH had the lowest 
      bioavailability regarding the aPTT, aXa, and aIIa activities. Enoxaparin 
      exhibited only low aIIa activity but the highest aXa activity. Unlike UFH and 
      enoxaparin, MMWH showed a high recovery of aIIa activity, which suggests that it 
      combines the high potency to inhibit thrombin that characterizes UFH with the 
      high bioavailability of the LMWHs. Consequently, substantially lower doses are 
      needed to bring about effects comparable to those of UFH and LMWH.
FAU - Alban, Susanne
AU  - Alban S
AD  - Institute of Pharmacy, University of Regensburg, Germany. 
      Susanne.Alban@chemie.uni-regensburg.de
FAU - Welzel, Dieter
AU  - Welzel D
FAU - Hemker, H Coenraad
AU  - Hemker HC
LA  - eng
PT  - Clinical Trial
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Semin Thromb Hemost
JT  - Seminars in thrombosis and hemostasis
JID - 0431155
RN  - 0 (Enoxaparin)
RN  - 0 (Factor Xa Inhibitors)
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - 9000-94-6 (Antithrombin III)
RN  - 9005-49-6 (Heparin)
SB  - IM
MH  - Adult
MH  - Antithrombin III/antagonists & inhibitors
MH  - Cross-Over Studies
MH  - Double-Blind Method
MH  - Enoxaparin/administration & dosage/pharmacokinetics
MH  - Factor Xa Inhibitors
MH  - Heparin/administration & dosage/*pharmacokinetics
MH  - Heparin, Low-Molecular-Weight/administration & dosage/pharmacokinetics
MH  - Humans
MH  - Male
MH  - Molecular Weight
MH  - Partial Thromboplastin Time
MH  - Pharmacokinetics
EDAT- 2002/09/24 06:00
MHDA- 2003/07/12 05:00
CRDT- 2002/09/24 06:00
PHST- 2002/09/24 06:00 [pubmed]
PHST- 2003/07/12 05:00 [medline]
PHST- 2002/09/24 06:00 [entrez]
AID - 10.1055/s-2002-34306 [doi]
PST - ppublish
SO  - Semin Thromb Hemost. 2002 Aug;28(4):369-78. doi: 10.1055/s-2002-34306.