Pharmaceutica Analytica Acta

Abstract

calix[4]arene C-145 Effects on Plasma Haemostasis

Chernyshenko VO, Korolova DS, Dosenko VЕ, Pashevin DO, Kalchenko VI, Pirogova LV, Chernyshenko TM, Lugovska OE, Kravchenko NА, Makogonenko YM, Lugovskoy EV and Komisarenko SV

Background: Calix[4]arene-methylene-bis-phosphonic acid C-192 and its sodium salt C-145 were shown to be efficient inhibitors of fibrin polymerization in vitro. In presented work we analyze the effects of сalix[4]arene C-145 on haemostasis in vivo. Methods: Parameters of coagulation system of rabbits intravenously injected with C-145 were monitored. We measured thrombin time (TT), ecamulin time (ET) and activated partial thromboplastin time (APTT), determined the levels of fibrinogen, prothrombin, protein C, PAI-1, monitored overall haemostatic potential before and after the injection. Results: C-145 was administrated intravenously in the dose of 7.5 mg/kg of rabbit weight. 4 hours after the injection the thrombin time and activated partial thromboplastin time of rabbit’s blood plasma were prolonged 2 and 1,5 times respectively. Such prolongation was observed after 24 hours as well. However, the total fibrinogen and prothrombin levels did not change. Parameters of fibrinolytic system (PAI-1, clot lysis half-time) and anticoagulant system (protein C) remained unchanged. Conclusions: Therefore we assumed that calix[4]arene C-145’s effects on haemostasis consisted in selective inhibition of fibrin polymerization and formation of three-dimensional fibrin network.