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This study investigated the absorption of low molecular weight heparin (LMWH) after oral administration 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.): t1/2, 1.82 +/- 0.23 h; V, 4.34 +/- 0.651; and CL, 28.0 +/- 6.2 ml min-1. 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-IIa and APTT activities in addition to its anti-Xa activity.

Multiple blood samples were collected over the first 15 min after an i.v. injection of 25 units/kg of heparin in four healthy subjects. Plasma heparin activity in each sample was determined by a chemical neutralization assay using polybrene and a bioassay based on activated partial thromboplastin time. Chemically assayed heparin declined much more rapidly than bioassayed heparin over the first 5-7 min after the dose. Subsequently, both heparin activity vs time curves declined with a similar terminal half-life. Slopes of the in vivo 1n APTT vs plasma heparin activity (determined by chemical neutralization) relationships were significantly greater than those of the corresponding in vitro relationships between 1n APTT vs heparin activity added to plasma. A possible explanation for these heparin assay differences is a rapid in vivo enhancement of the anticoagulant effect of heparin. How such enhancement may occur, however, is presently unclear.