THE EFFECT OF UNFRACTIONATED HEPARIN ON LYMPHATIC DRAINAGE OF TISSUES AND PHARMACOKINETICS OF CEFOTAXIM

Abstract

Over the past decades, methods of targeted delivery of drugs to target tissues through the lymphatic system have been intensively developed, which makes it possible to create and maintain adequate concentrations of drugs. It has special meaning and impotence during the therapy antibiotic therapy of infectious and inflammatory processes. In this regard, the experimental study of pharmacological properties of drugs that enhance lymphatic drainage of tissues and at the same time promote the transport of antibiotics into the lymphatic system has natural interest. We studied the effect of unfractionated heparin sodium on lymphatic flow rate in tissues, the level of the β-lactam antibiotic cefotaxime in rabbit and mouse blood plasma and its concentration in mouse liver and intestinal tissues in experiments. Heparin sodium proved to be effective in stimulating lymphatic flow and facilitating endolymphatic delivery of the antibiotic. The administration of cefotaxime after an injection of heparin sodium led to the increased concentration of the antibiotic in rabbit blood plasma at all time points of the study (in an hour and a half and in 3 hours, in four and a half hours and in 6 hours, in 8, 12 and 24 hours), as well as the increased antibiotic level in mouse blood plasma and intestinal tissue in an hour and a half and in 24 hours after the injection. The cefotaxime level in liver tissue did not change, while its concentration ratio between liver tissue and blood plasma was falling, which suggests that the hepatic extraction of cefotaxime decreased. Considering the obtained evidence, we can recommend the clinical use of heparin sodium in lymphotropic therapy to facilitate endolymphatic delivery.