Increased plasma anti-Xa activity and recovery of heparin from urine suggest absorption of orally administered unfractionated heparin in human subjects

Although heparin is not generally administered orally, the results of studies involving rats suggest that heparin is absorbed, with low levels in plasma but extensive distribution to the endothelium. To determine whether evidence of absorption after oral administration can also be demonstrated in human subjects, we administered unfractionated porcine heparin in a single dose of 1000 U/kg to 6 healthy human subjects. Plasma anticoagulant activity was monitored between 5 minutes and 72 hours after administration, and chemical heparin concentrations were determined in 24-hour urine samples for as long as 120 hours after administration. Plasma anticoagulant activity, determined by anti-Xa activity, increased as soon as 5 minutes after heparin administration, peaked at 120 minutes, and was still increased 72 hours after administration. Values were significantly greater 15 minutes to 48 hours after administration compared with values before administration (paired t test). Mean activated partial thromboplastin time and Heptest values in subjects given heparin were greater than those in controls 15 and 30 minutes and 5 to 120 minutes after administration, respectively. Heparin was recovered from urine as long as 120 hours after administration (the latest time point at which samples were collected); greater amounts were excreted between 48 and 120 hours than before 48 hours. Recovery from both plasma and urine suggest that unfractionated heparin administered orally is absorbed in human subjects, is widely distributed, and is found in the body at least 120 hours after administration. Because heparin is readily bound to endothelium, recovery from plasma and urine likely reflect considerable amounts with endothelium, as has been observed in other species.