Pharmacokinetics of the low molecular weight heparin Fragmin (R) D in dogs

The pharmacokinetics of a low molecular weight heparin (LMWH; Fragmin(R) D) was studied in dogs after intravenous and subcutaneous administration, bas ed on antifactor Xa- (anti-fXa-) activity. Each dosage was examined in 5 ad ult Beagles. After intravenous application of 25, 50 and 100 anti-fXaU./kg body weight (BW) the mean peak plasma heparin activity of 0.52 +/- 0.12 ((x ) over bar +/- s), 1.08 +/- 0.23 and 1.86 +/- 0.17 anti-fXaU./ml, respectiv ely, was measured. After subcutaneous application of 50, 100 and 200 anti-f XaU./kg BW maximum heparin activity in the plasma was determined after 144- 216 minutes (mean values) of 0.28 +/- 0.01, 0.52 +/- 0.06 or 1.09 +/- 0.20 anti-fXaU./ml. Intravenous application of LMWH has a short plasma terminal half-life (t(50)) between 49 and 76 minutes which depended on the dosage. A fter administration of 50 anti-fXaU./kg BW (74 minutes) and 100 anti-fXaU./ kg BW (76 minutes) no essential difference was shown. A distinctly longer t (50) was found after subcutaneous injection. After injection of 50, 100 and 200 anti-fXaU./kg BW t(50) values of 81, 123 and 182 minutes were calculat ed. According to this, with increasing dosage a decrease of the total clear ance was found for both application routes. The apparent volume of distribu tion after intraveneously applicated LMWH ranged between 50 and 70 ml/kg BW . The absolute bioavailability calculated for the subcutaneous NMH-injectio n of 50 and 100 anti-fXaU./kg BW was 107 % and 104 %, respectively.