PMID- 18264127
OWN - NLM
STAT- MEDLINE
DCOM- 20080515
LR  - 20211020
IS  - 0007-1188 (Print)
IS  - 1476-5381 (Electronic)
IS  - 0007-1188 (Linking)
VI  - 153
IP  - 6
DP  - 2008 Mar
TI  - Enhanced antithrombotic effects of unfractionated heparin in rats after repeated 
      oral doses and its relationship to endothelial heparin concentration.
PG  - 1177-84
LID - 10.1038/bjp.2008.14 [doi]
AB  - BACKGROUND AND PURPOSE: An oral, single dose of 7.5 mg kg(-1) of unfractionated 
      heparin (UFH) reduces thrombosis by 50% in a rat model of venous thrombosis. As 
      long-term use is required clinically, our objectives were to study the 
      antithrombotic effects following repeated oral UFH administration. EXPERIMENTAL 
      APPROACH: Bovine lung UFH was administered by oral gavage to rats in 3 doses of 
      7.5 mg kg(-1) each 12, 24, 48, and 72 h apart; and in 3 or 15 doses of 1 mg 
      kg(-1) every 48 h. The last dose was given immediately after thrombus initiation 
      where 10% formalin in methanol was applied to the jugular vein. The vessel was 
      examined for thrombosis 4 h later. Amounts of heparin in tissue and endothelium, 
      and plasma anticoagulant activity were measured. KEY RESULTS: When 3 x 7.5 mg 
      kg(-1) heparin was given, thrombotic incidence was most reduced at 48 h 
      dose-intervals and was significantly less than single dose treatment. There was a 
      negative correlation between endothelial heparin content and thrombotic 
      incidence, but not anticoagulant activity. When 3 doses of 1 mg kg(-1) every 48 h 
      were given, thrombotic incidence was similar to single dose treatment. When 15 
      doses were given, total thrombotic incidence was less than for 3 doses and was 
      similar to that after s.c. administration. CONCLUSIONS AND IMPLICATIONS: 
      Antithrombotic activity increased with repeated doses of oral UFH, with 
      antithrombotic effects similar to s.c. administration. Antithrombotic activity 
      was related to heparin on endothelium.
FAU - Hiebert, L M
AU  - Hiebert LM
AD  - Western College of Veterinary Medicine, Department of Veterinary Biomedical 
      Sciences, University of Saskatchewan, Saskatchewan, Saskatoon, Canada. 
      linda.hiebert@usask.ca
FAU - Ping, T
AU  - Ping T
FAU - Wice, S M
AU  - Wice SM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080211
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Anticoagulants)
RN  - 9005-49-6 (Heparin)
SB  - IM
MH  - Administration, Oral
MH  - Animals
MH  - Anticoagulants/administration & dosage/pharmacokinetics/*pharmacology
MH  - Cattle
MH  - Disease Models, Animal
MH  - Drug Administration Schedule
MH  - Endothelium, Vascular/metabolism
MH  - Heparin/administration & dosage/pharmacokinetics/*pharmacology
MH  - Injections, Subcutaneous
MH  - Male
MH  - Rats
MH  - Rats, Wistar
MH  - Thrombosis/*drug therapy
MH  - Tissue Distribution
PMC - PMC2275434
EDAT- 2008/02/12 09:00
MHDA- 2008/05/16 09:00
PMCR- 2009/03/01
CRDT- 2008/02/12 09:00
PHST- 2008/02/12 09:00 [pubmed]
PHST- 2008/05/16 09:00 [medline]
PHST- 2008/02/12 09:00 [entrez]
PHST- 2009/03/01 00:00 [pmc-release]
AID - bjp200814 [pii]
AID - 10.1038/bjp.2008.14 [doi]
PST - ppublish
SO  - Br J Pharmacol. 2008 Mar;153(6):1177-84. doi: 10.1038/bjp.2008.14. Epub 2008 Feb 
      11.