PMID- 14993814
OWN - NLM
STAT- MEDLINE
DCOM- 20050103
LR  - 20190719
IS  - 0918-6158 (Print)
IS  - 0918-6158 (Linking)
VI  - 27
IP  - 3
DP  - 2004 Mar
TI  - Studies on the intestinal absorption of low molecular weight heparin using 
      saturated fatty acids and their derivatives as an absorption enhancer in rats.
PG  - 418-21
AB  - Intestinal absorption of low molecular weight heparin (LMWH) as well as 
      unfractionated heparin (UFH) is limited due to its large molecular size and 
      extensive negative charge. Development of its oral formulations would allow 
      outpatient treatment with LMWH and UFH, and contribute a reduction in hospital 
      expenses. The present study was aimed at evaluating the absorption enhancers 
      Labrasol and Gelucire 44/14, which mainly consist of glycerides and fatty acids 
      esters, to improve the intestinal absorption of LMWH. The absorption effects of 
      saturated fatty acids with several carbon chain lengths (C6-C14) were also 
      investigated. LMWH formulated with or without absorption enhancer was 
      administered to the duodenum of fasted rats. The doses of LMWH and absorption 
      enhancer were 20 mg/kg and 30 mg/kg, respectively. Plasma anti-Xa activity was 
      measured as a marker of the LMWH absorption. By administration of the LMWH 
      formulation with Labrasol but not with Gelucire 44/14, the plasma anti-Xa 
      activity was increased to a level above 0.2 IU/ml which is the critical level for 
      elucidation of its anticoagulant activity. Saturated fatty acids also enhanced 
      the intestinal absorption of LMWH, and the order of absorption-enhancing effect 
      was C10=C12>C14>C16>C8> or =C6. These results suggest that the intestinal 
      absorption of LMWH varies with carbon chain lengths of the saturated fatty acids.
FAU - Mori, Saori
AU  - Mori S
AD  - Shimizu Research Center, Shimizu Pharmaceutical Co., Ltd., Shimizu Miyakami, 
      Shizuoka, Japan. saori_mori@ajinomoto.com
FAU - Matsuura, Akihiro
AU  - Matsuura A
FAU - Rama Prasad, Yarasani Venkata
AU  - Rama Prasad YV
FAU - Takada, Kanji
AU  - Takada K
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - Japan
TA  - Biol Pharm Bull
JT  - Biological & pharmaceutical bulletin
JID - 9311984
RN  - 0 (Adjuvants, Pharmaceutic)
RN  - 0 (Anticoagulants)
RN  - 0 (Emulsions)
RN  - 0 (Factor Xa Inhibitors)
RN  - 0 (Fatty Acids)
RN  - 0 (Glycerides)
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - 0 (Organic Chemicals)
RN  - 00BT03FSO2 (Labrasol)
RN  - 121548-04-7 (gelucire 44-14)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - M316WT19D8 (parnaparin)
SB  - IM
MH  - Adjuvants, Pharmaceutic/*pharmacology
MH  - Animals
MH  - Anticoagulants/*pharmacokinetics
MH  - Duodenum/metabolism
MH  - Emulsions/pharmacology
MH  - Factor Xa Inhibitors
MH  - Fatty Acids/*pharmacology
MH  - Glycerides
MH  - Heparin, Low-Molecular-Weight/*pharmacokinetics
MH  - Intestinal Absorption/*drug effects
MH  - Male
MH  - Organic Chemicals
MH  - Polyethylene Glycols/pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Time Factors
EDAT- 2004/03/03 05:00
MHDA- 2005/01/04 09:00
CRDT- 2004/03/03 05:00
PHST- 2004/03/03 05:00 [pubmed]
PHST- 2005/01/04 09:00 [medline]
PHST- 2004/03/03 05:00 [entrez]
AID - 10.1248/bpb.27.418 [doi]
PST - ppublish
SO  - Biol Pharm Bull. 2004 Mar;27(3):418-21. doi: 10.1248/bpb.27.418.