Intraduodenal absorption in the rabbit of a novel heparin salt.
The intraduodenal absorption of a new low-molecular-weight heparin (LMWH) diamine salt (ITF 1331) was compared with the parent compound ITF 1060 and with sodium LMWH, in anaesthetized rabbits. The administration of either salt, but not of sodium LMWH, resulted in a dose-related increase in plasma anti-Xa activity. In this respect ITF 1331 was slightly superior to ITF 1060, and in acute-toxicity studies the counterion itself (ITF 258) was less toxic than that in ITF 1060 (counterion No. 4). These data confirm that a tertiary diamine within the counterion is an important structural requirement for the bioavailability of heparin by the intraduodenal route, and suggest that ITF 1331 may represent an important advance in the search for an oral heparin.
Andriuoli
G
G
Italfarmaco Research Center, Cinisello Balsamo, Milan, Italy.
Caramazza
I
I
Galimberti
G
G
Zoppetti
G
G
Benedini
F
F
Sala
A
A
Del Soldato
P
P
D000818:Animals; D001682:Biological Availability; D002082:Butylamines / Q000633:toxicity; D004386:Duodenum / Q000378:metabolism*; D065427:Factor Xa Inhibitors; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000633:toxicity; D007408:Intestinal Absorption; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D011817:Rabbits / Q000378:metabolism*; D013329:Structure-Activity Relationship
D002082:Butylamines; D065427:Factor Xa Inhibitors; D006495:Heparin, Low-Molecular-Weight; C077701:ITF 258; C077704:ITF 1331