Investigations on plasma activity of low molecular weight heparin after intravenous and oral administrations.

Abstract

This study investigated the absorption of low molecular weight heparin (LMWH) after oral administrati6n in man. Six healthy subjects received 5,000 anti-Xa units of LMWH (Kabi 2165) by both i.v. and oral administration. The oral formulations were prepared in pH 4.0 and pH 7.0 buffered solutions. Multiple blood samples were collected after each dose for measurements of anti-Xa, anti-IIa and APTT plasma heparin activities. Pharmacokinetic parameters based on the anti-Xa activity measurements after the i.v. dose were as follows (mean ± s.d.): t½, 1.82 ± 0.23 h; V, 4.34 ± 0.651; and CL, 28.0 ± 6.2 ml min . Half-life values based on the anti-IIa and APTT activities were 1.63 ± 0.43 and 1.09 + 0.51 h, respectively. Considerable prolongations in APTT were observed, with APTT at 30 min averaging 55.7 ± 4.1 s (1.84 ± 0.27 times baseline values). After oral administration, no measurable plasma heparin activities were observed with either LMWH preparation. The results of this investigation indicate that LMWH does not have detectable plasma activity after oral administration, and that after i.v. administration it has significant anti-Ila and APTT activities in addition to its anti-Xa activity.

Excretion of low molecular weight heparin in human milk

“…Dryjski et al. [8] observed no measurable plasma activity in patients given LMWH orally at a dose of 5000 anti‐Xa units. In a study in rats, antithrombotic activity was seen following oral doses of roughly 5000–10 000 IU kg −1 of body weight [9].…”

Movement of Heparins Across Rat Gastric Mucosa is Dependent on Molecular Weight and pH

“…They are believed not to be effective when administered orally (1). These assumptions are based on the observations that little or no change is seen in anticoagulant activity following oral administration of heparins (17) or heparins are too highly Fig. 2.…”

Enhanced antithrombotic effects of unfractionated heparin in rats after repeated oral doses and its relationship to endothelial heparin concentration

“…Although heparin is considered to be ineffective when given by the oral route, our laboratory and others have collected considerable data supporting the hypothesis that heparin is absorbed, without delivery agents ( Gorski and Lagodzinski, 1991 ; Engelberg, 1995 ; Hiebert, 2002 ). Oral heparin is considered ineffective due to certain facts: it is believed that heparin is degraded by stomach acids ( Money and York, 2001 ); the high negative charge and molecular weight suggest that absorption is unlikely ( Money and York, 2001 ); there is little change in anticoagulant activity following oral administration ( Dryjski et al , 1989 ). However, it is unlikely that heparin is broken down by stomach acidity since heparin in 0.1 N HCl at 30 °C for 100 h showed no degradation, while in 0.1N HCl at 60 °C for 10 h showed only 2% breakdown ( Jandik et al , 1996 ).…”

“…The high negative charge and size of the heparin molecule and the low pH as well as digestive enzymes in the gut have led to the assumption that heparin is unsuitable for absorption ( Arbit et al , 2006 ). Little change in anticoagulant activity following oral administration also supports this assumption ( Dryjski et al , 1989 ). However, our studies show that oral heparins prevent thrombosis in rat venous and arterial thrombosis models ( Hiebert et al , 1996 , 2000a , 2001 ; Pinel et al , 2004 ).…”