Pharmacokinetics of an unfractionated heparin (Liquemin (R)) in the dog after intravenous and subcutaneous application based on heparin-activity

In this study pharmacokinetic data for the unfractionated heparin Liquemin( R) were obtained after intravenous and subcutaneous application. Each dosag e was examined in 5 healthy, adult Beagle dogs. After intravenous applicati on of 25, 50 and 100 I.U./kg body weight heparin plasma activity of 0.65 +/ - 0.15 I.U./ml (mean +/- s), 0.91 +/- 0.10 I.U./ml and 1.94 +/- 0.22 I.U./m l was measured. Subcutaneous applications of 250, 500 or 750 I.U./kg reveal ed maximum plasma heparin activities of 0.25 +/- 0.10, 0.60 +/- 0.15 and 1. 29 +/- 0.24 I.U./ml. The maximum heparin activity in the plasma was observe d after 3.8 +/- 1.1 (250 und 500 I.E/kg) or 4.0 +/- 1.0 hours (750 I.E./kg) , respectively. Intravenously applicated heparin has a short terminal half- life time (t(50)) between 22 and44 minutes. The t(50) after subcutaneous ap plication of heparin was distinctly longer. After 250, 500 or 750 I.U./kg t he t(50) was 3.7 +/- 2.4, 3.5 +/- 1.2 or 5.3 +/- 2.4 hours. Corresponding t o this result a lower total clearance (CItot) was found with increasing dos es. Especially the Cl, after subcutaneous injection decreased from 2.08 +/- 0.73 ml/min/kg (250 I.E./kg) to 0.83 +/- 0.27 ml/min/kg (750 I.E./kg). The volume of distribution of heparin corresponded approximately to the plasma volume. The total bioavailability of subcutaneously administered UFH was 5 3-100 % depending on the dosage.