HYALURONIDASE: AN EXPERIMENTAL CONFIRMATION OF THE PROPERTIES OF THE ENDOLYMPHATIC CONDUCTOR

Abstract

One of the major achievements of contemporaneous pharmacology is the clinical implementation of the agents (the so called “endolymphatic conductors”) that allow for targeted delivering of antibiotic into the lymphatic system. Their use provides the basis for the lymphotropic treatment method that has been implemented into various areas of medical practice. Hyaluronidase is the most known agent used for this purpose. It has been shown that its preliminary administration before the injection of an antibiotic can improve clinical efficacy of the treatment; however, there is a need in the experimental validation of this approach to antibacterial therapy. The study was aimed at evaluation of hyaluronidase effects on the rate of lymphatic drainage of tissues and cefotaxime pharmacokinetics. We measured the time of elimination of lymphotropic Evans blue dye from the mouse mesentery when administered against the background of hyaluronidase, changes in cefotaxime levels over 24 hours in rabbit plasma and in mice plasma, gut tissues and liver at 1,5 and 24 hours after combined administration of hyaluronidase and the antibiotic. In addition, we calculated the liver to plasma ratio for the antibiotic concentrations. The data obtained shows that hyaluronidase can stimulate tissue lymphatic drainage. Its preliminary administration results in higher cefotaxime levels in rabbit and mice plasma at all time points of the study, compared to cefotaxime monotherapy, with prolongation of its systemic circulation of up to 24 hours. The use of cefotaxime after hyaluronidase leads to an increase of its levels in the mice gut tissues both at 1,5 and 24 hours, but has no effect on the antibiotic accumulation in the liver of the animals. However, the calculated liver to plasma blood ratio of cefotaxime after the administration of hyaluronidase is significantly lower than in the animals with the antibiotic monotherapy. This may indirectly indicate to a decrease in the hepatic extraction of the antibiotic when administered with hyaluronidase. The study results confirm that hyaluronidase has the properties of a lymphatic stimulator and an endolymphatic conductor for the water-soluble antibiotic cefotaxime.