Structural requirements for duodenal permeability of heparin-diamine complexes.
We have compared the physico-chemical behaviors alone and in the presence of a synthetic bilayer membrane, in aqueous solution and the bioavailability after intraduodenal administration to rabbits, of the two heparin diamine salts ITF-300 and ITF-331 with those of the heparin-amine salt ITF-1175. The three salts have similar structures but different characteristics of compounds tend to form aggregates in solution, but at different critical concentrations. The compounds induce fusion of single-walled vesicles of a synthetic peptide lipid into multi-walled lamellae. The minimal concentrations of the compounds required for the formation of such lamellae differ. This behavior in solution explains the differences in absorption in the animal model. This makes it possible to correlate enhanced heparin bioavailability with the structural nature of the diamine counter-ions used to prepare heparin salts.
Zoppetti
G
G
Italfarmaco Research Center, Milan, Italy.
Caramazza
I
I
Murakami
Y
Y
Ohno
T
T
D000818:Animals; D015195:Drug Design; D004386:Duodenum / Q000378:metabolism*; D006493:Heparin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000378:metabolism; D007408:Intestinal Absorption; D008297:Male; D008954:Models, Biological; D010539:Permeability; D011817:Rabbits; D012996:Solutions; D013329:Structure-Activity Relationship
C078970:ITF 1175; C078969:ITF 331; D012996:Solutions; C078918:ITF 300; D006493:Heparin