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CD5000 heparin (LMWH) is a low molecular weight heparin fraction, ave. mol wt. ∼ 5100. Plasma levels of antiFactor Xa activity (XaA) after iv, pulmonary, sc and oral administration of LMWH and commercial heparin (CH) were examined in rats, rabbits and dogs. Overall, LMWH maintained higher levels of XaA in plasma than did a similar mg dose of CH. When the heparins were given iv, plasma XaA after LMWH had a t1/2 ∼ 2X as long as that after CH. When similar mg doses were given sc, the average plasma XaA following LMWH was significantly higher than that following CH during 0-6 hrs postdose. When equal USP unit doses (four times as much LMWH on a mg basis) were administered into the lungs of dogs, LMWH showed plasma XaA significantly higher than after CH. LMWH also showed higher plasma XaA on oral administration of equal USP unit doses in rats, but the fraction of the dose absorbed and the plasma levels were low. About 4X as much LMWH on a mg basis as CH had to be given to achieve similar APTT values in dog plasma. LMWH may have significant therapeutic advantages in man if pharmacokinetic differences and different blood coagulation effects of the various mol wt. heparins described here in animals also occur in man. Studies in humans are planned.

thrombosis and haemostasis

Anti Factor Xa Activity In Plasma Following Oral, Pulmonary, Subcutaneous And Intravenous Administration Of Cd5000 Low Molecular Weight Heparin And Commercial Heparin To Rats, Rabbits And Dogs