PMID- 11251329
OWN - NLM
STAT- MEDLINE
DCOM- 20010802
LR  - 20171101
IS  - 0301-0147 (Print)
IS  - 0301-0147 (Linking)
VI  - 30
IP  - 5
DP  - 2000 Sep-Oct
TI  - Intestinal absorption of low molecular weight heparin in animals and human 
      subjects.
PG  - 225-32
AB  - INTRODUCTION: We had previously shown that the use of bile salts, which act as 
      surfactants, facilitates the intestinal absorption of large molecules such as 
      those of heparin and insulin. However, the bioavailability of unfractionated 
      heparin (UFH) administered through the large intestine was low. The aim of the 
      present study was to evaluate the absorption of low molecular weight heparin 
      (LMWH) combined with bile salts through the gut mucosa in animals and human 
      subjects. MATERIALS AND METHODS: LMWH (Fragmin, Kabi-Pharmacia, Stockholm) or UFH 
      with or without sodium cholate (Sch) was administrated rectally in rats and 
      healthy volunteers via a microenema. Absorption was estimated by the activated 
      partial thromboplastin time (aPTT), the plasma anti-factor Xa activity and the 
      plasma lipoprotein lipase (LPL) activation. RESULTS: In groups of 6 rats, LMWH at 
      doses of 100--1,000 U with sodium cholate (10--20 mg/ml) was readily absorbed 
      through the gut mucosa, as indicated by both, anti-factor Xa levels of up to 1 
      U/ml and a dose-dependent activation of LPL. The absorption was significantly 
      superior to that of UFH with Sch or LMWH given without Sch (p < 0.001). The 
      plasma anti-factor Xa levels in the 6 healthy volunteers who received a 
      microenema containing 25,000 U of LMWH with 20 mg/ml of Sch were 0.38 U/ml at 15 
      min and 0.1 U/ml at 240 min. LPL activation and aPTT prolongation were also 
      observed in these subjects. The plasma LMWH levels after rectal application were 
      in the same range as those obtained after subcutaneous administration, however 
      the elimination time (t 1/2) was shorter. There were no adverse reactions. 
      CONCLUSIONS: Intestinal absorption of LMWH facilitated by Sch is both feasible 
      and safe. A slow release formulation will be needed to prolong the plasma 
      half-life.
CI  - Copyright 2001 S. Karger AG, Basel
FAU - Nissan, A
AU  - Nissan A
AD  - Department of Hematology, Hadassah University Hospital, Jerusalem, Israel.
FAU - Ziv, E
AU  - Ziv E
FAU - Kidron, M
AU  - Kidron M
FAU - Bar-On, H
AU  - Bar-On H
FAU - Friedman, G
AU  - Friedman G
FAU - Hyam, E
AU  - Hyam E
FAU - Eldor, A
AU  - Eldor A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Switzerland
TA  - Haemostasis
JT  - Haemostasis
JID - 0371574
RN  - 0 (Anticoagulants)
RN  - 0 (Bile Acids and Salts)
RN  - 0 (Drug Combinations)
RN  - 0 (Factor Xa Inhibitors)
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - EC 3.1.1.34 (Lipoprotein Lipase)
RN  - NU3Y4CCH8Z (Sodium Cholate)
RN  - S79O08V79F (Dalteparin)
SB  - IM
MH  - Administration, Rectal
MH  - Adult
MH  - Animals
MH  - Anticoagulants/administration & dosage/blood/pharmacokinetics
MH  - Bile Acids and Salts/administration & dosage/pharmacology
MH  - Biological Availability
MH  - Dalteparin/administration & dosage/blood/pharmacokinetics
MH  - Dose-Response Relationship, Drug
MH  - Drug Combinations
MH  - Enzyme Activation/drug effects
MH  - Factor Xa Inhibitors
MH  - Female
MH  - Heparin, Low-Molecular-Weight/administration & dosage/blood/*pharmacokinetics
MH  - Humans
MH  - Intestinal Absorption/*drug effects
MH  - Intestinal Mucosa/metabolism
MH  - Lipoprotein Lipase/metabolism
MH  - Male
MH  - Rats
MH  - Sodium Cholate/administration & dosage/pharmacology
EDAT- 2001/03/17 10:00
MHDA- 2001/08/03 10:01
CRDT- 2001/03/17 10:00
PHST- 2001/03/17 10:00 [pubmed]
PHST- 2001/08/03 10:01 [medline]
PHST- 2001/03/17 10:00 [entrez]
AID - 54138 [pii]
AID - 10.1159/000054138 [doi]
PST - ppublish
SO  - Haemostasis. 2000 Sep-Oct;30(5):225-32. doi: 10.1159/000054138.