PMID- 19888526
OWN - NLM
STAT- MEDLINE
DCOM- 20100315
LR  - 20141120
IS  - 2567-689X (Electronic)
IS  - 0340-6245 (Linking)
VI  - 102
IP  - 5
DP  - 2009 Nov
TI  - M118--a rationally engineered low-molecular-weight heparin designed specifically 
      for the treatment of acute coronary syndromes.
PG  - 900-6
LID - 10.1160/TH09-02-0105 [doi]
AB  - The initial choice of anticoagulant therapy administered in emergency departments 
      for acute coronary syndromes (ACS) has important consequences for subsequent 
      patient care, as neither unfractionated heparin (UFH) nor low-molecular-weight 
      heparin (LMWH) are ideally suited for all potential clinical treatment pathways. 
      UFH remains widely used for surgical interventions because of the ability to 
      rapidly reverse its anticoagulant activity. However, the unpredictable 
      pharmacokinetic profile of UFH presents safety issues, and the low subcutaneous 
      bioavailability limits the utility of UFH for patients who are medically managed. 
      LMWH has superior pharmacokinetic properties, but its anticoagulant activity 
      cannot be effectively monitored or reversed during surgery. There is an unmet 
      medical need for a baseline anticoagulant therapy that addresses these 
      shortcomings while retaining the beneficial properties of both UFH and LMWH. We 
      describe here M118, a novel LMWH designed specifically for use in the treatment 
      of ACS. M118 shows broad anticoagulant activity, including potent activity 
      against both factor Xa (~240 IU/mg) and thrombin (factor IIa; ~170 IU/mg), low 
      polydispersity, high (78%) subcutaneous bioavailability in rabbits, and 
      predictable subcutaneous and intravenous pharmacokinetics. Additionally, the 
      anticoagulant activity of M118 is monitorable by standard coagulation assays and 
      is reversible with protamine. M118 demonstrates superior activity to conventional 
      LMWH in a rabbit model of abdominal arterial thrombosis without increasing 
      bleeding risk, and is currently being evaluated in a phase II clinical trial 
      evaluating efficacy and safety in patients undergoing percutaneous coronary 
      intervention.
FAU - Kishimoto, Takashi Kei
AU  - Kishimoto TK
AD  - Momenta Pharmaceuticals, Inc, Cambridge, MA 02142, USA. 
      kkishimoto@momentapharma.com
FAU - Qi, Yi Wei
AU  - Qi YW
FAU - Long, Alison
AU  - Long A
FAU - Capila, Ishan
AU  - Capila I
FAU - Sasisekharan, Ram
AU  - Sasisekharan R
FAU - Guerrero, Luis
AU  - Guerrero L
FAU - Fier, Ian
AU  - Fier I
FAU - Roach, James
AU  - Roach J
FAU - Venkataraman, Ganesh
AU  - Venkataraman G
LA  - eng
PT  - Journal Article
PL  - Germany
TA  - Thromb Haemost
JT  - Thrombosis and haemostasis
JID - 7608063
RN  - 0 (Anticoagulants)
RN  - 0 (Factor Xa Inhibitors)
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - EC 3.4.21.5 (Thrombin)
SB  - IM
MH  - Acute Coronary Syndrome/*drug therapy
MH  - Animals
MH  - Anticoagulants/administration & dosage/chemistry/isolation & 
      purification/pharmacology/*therapeutic use/toxicity
MH  - Aorta, Abdominal
MH  - Aortic Diseases/*drug therapy
MH  - Arterial Occlusive Diseases/*drug therapy
MH  - Biological Availability
MH  - Disease Models, Animal
MH  - Drug Design
MH  - Drug Evaluation, Preclinical
MH  - Factor Xa Inhibitors
MH  - Hemorrhage/chemically induced
MH  - Heparin, Low-Molecular-Weight/administration & dosage/chemistry/isolation & 
      purification/therapeutic use/toxicity
MH  - Injections, Intravenous
MH  - Injections, Subcutaneous
MH  - Intestinal Mucosa/chemistry
MH  - Male
MH  - Rabbits
MH  - Swine
MH  - Thrombin/antagonists & inhibitors
EDAT- 2009/11/06 06:00
MHDA- 2010/03/17 06:00
CRDT- 2009/11/06 06:00
PHST- 2009/11/06 06:00 [entrez]
PHST- 2009/11/06 06:00 [pubmed]
PHST- 2010/03/17 06:00 [medline]
AID - 09-02-0105 [pii]
AID - 10.1160/TH09-02-0105 [doi]
PST - ppublish
SO  - Thromb Haemost. 2009 Nov;102(5):900-6. doi: 10.1160/TH09-02-0105.