Altered pharmacokinetic properties of a lipophilically derivatized low-molecular-weight heparin in rats.

摘要: A new generation of lipophilic heparins has been developed that show longer-lasting inhibitory effects on the coagulation system. We have studied radiopharmacokinetics a derivatized low-molecular-weight heparin (LMWH) with residualizing tyramine-deoxysorbitol label in comparison conventional LMWH after intravenous application into Wistar rats. Whole body scintigraphy and analysis blood organ distribution different tracer preparations revealed lipophilically substance was predominantly trapped liver RES by scavenger receptor-mediated mechanism. After saturable uptake mechanism blocked maleylated bovine serum albumin, 41.4% circulated blood, as compared 18.4% control 1% LMWH. The same results were attained competition experiment an excess unfractionated heparin. Urinary excretion among rats this considerably lower (13.7%) (53.0%). Experiments bound nonspecifically to rat albumin confirmed prolonged half-life might part be due increased affinity for albumin. About 59% activity found reticuloendothelial system, only 3.3% excreted urine 3 hours injection. Further studies are necessary evaluate accumulation rates metabolic fate case impeded system before attempts made therapeutically apply these compounds.