Tissue distribution and antithrombotic activity of unlabeled or C-14-labeled porcine intestinal mucosal heparin following administration to rats by the oral route

Distribution and antithrombotic activity of orally administered unfractiona ted porcine heparin were studied. [C-14]Heparin was prepared by de-N-acetyl ation of porcine mucosal heparin followed by re-N-acetylation, using [C-14] acetic anhydride. [C-14]Heparin and (or) cold heparin (60 mg/kg) were admin istered by stomach tube to male Wistar rats. Blood, all levels of gut and g ut contents, liver, lung, spleen, kidney, and aortic and vena caval endothe lium were collected under deep anesthesia at 3, 6, 15, 30, and 60 min and 4 and 24 h (6 rats/group) after administration. Urine and feces were collect ed at 24 h, using metabolic cages. In three additional rats, drugs were adm inistered in gelatin capsules. Tissues listed above and tongue, esophagus, trachea, brain, heart, thymus, bile ducts, vena caval and aortic walls, ure ters, bladder, samples of muscle, skin, hair, and bone marrow were collecte d at 24 h. Radioactivity and chemical heparin, measured by agarose gel elec trophoresis, were observed in all tissues examined as well as gut washes, p lasma, urine, and feces. Radiolabel recovered was confirmed to be heparin b y autoradiograms of gradient polyacrylamide electrophoretic gels. [C-14]Hep arin and chemical heparin in gut tissue suggest a transit time of 4 h. Porc ine or bovine heparin (7.5 mg/kg), administered by stomach tube, decreased the incidence of thrombosis induced by applying 10% formalin in 65% methano l to the exposed jugular vein of rats. Heparin isolation from non-gut tissu e, endothelium, urine, and plasma and the observed antithrombotic effect ar e consistent with oral bioavailability.