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

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. 1989 The British Pharmacological Society