PMID- 11060763
OWN - NLM
STAT- MEDLINE
DCOM- 20010108
LR  - 20190915
IS  - 1354-3784 (Print)
IS  - 1354-3784 (Linking)
VI  - 9
IP  - 7
DP  - 2000 Jul
TI  - Recent advances in clinical trials of the direct and indirect selective Factor Xa 
      inhibitors.
PG  - 1595-600
AB  - Over the years, pharmacological intervention to prevent undesired intravascular 
      coagulation and the associated detrimental effects has been a clinical challenge. 
      The first generation of anticoagulant agents, warfarin and unfractionated heparin 
      (UFH), involve indirect mechanisms of inhibiting the coagulation cascade. 
      Fractionated, or low-molecular weight, heparins (LMWHs) are more selective for 
      coagulation Factor Xa (FXa) over thrombin (FIIa). LMWHs also utilise an indirect 
      mechanism of inhibition and have improved pharmacokinetic, pharmacodynamic and 
      therapeutic profiles over UFH. The success of LMWHs, along with the pivotal 
      location of FXa in the coagulation cascade, has prompted interest in the 
      discovery and development of selective FXa inhibitors. There are two general 
      classes of FXa inhibitors in development, of which SR90107A/ORG31540, an 
      antithrombin-III-dependent pentasaccharide and DX-9065a, a small molecule direct 
      FXa inhibitor, have published clinical data. SR90107A/ORG31540 and DX-9065a offer 
      safe, predictable pharmacokinetic and pharmacodynamic profiles when administered 
      subcutaneously and intravenously, respectively, to healthy volunteers and appear 
      to be progressing through clinical development. The purpose of this review is to 
      compile and summarise the published Phase I and II clinical data for 
      SR90107A/ORG31540 and DX-9065a.
FAU - Porcari, A R
AU  - Porcari AR
AD  - Information Research & Analysis, Department of Knowledge Management Services, 
      Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, 2800 
      Plymouth Road, Ann Arbor, Michigan 48105, USA. Anthony.Porcari@wl.com.
FAU - Chi, L
AU  - Chi L
FAU - Leadley, R
AU  - Leadley R
LA  - eng
PT  - Journal Article
PT  - Review
PL  - England
TA  - Expert Opin Investig Drugs
JT  - Expert opinion on investigational drugs
JID - 9434197
RN  - 0 (Blood Coagulation Factor Inhibitors)
RN  - 0 (Factor Xa Inhibitors)
RN  - 0 (Polysaccharides)
SB  - IM
MH  - Animals
MH  - Blood Coagulation Disorders/*drug therapy
MH  - Blood Coagulation Factor Inhibitors/*therapeutic use
MH  - *Factor Xa Inhibitors
MH  - Humans
MH  - Polysaccharides/therapeutic use
RF  - 16
EDAT- 2000/11/04 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/11/04 11:00
PHST- 2000/11/04 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/11/04 11:00 [entrez]
AID - 10.1517/13543784.9.7.1595 [doi]
PST - ppublish
SO  - Expert Opin Investig Drugs. 2000 Jul;9(7):1595-600. doi: 
      10.1517/13543784.9.7.1595.