Cholephilic characteristics of a new cytostatic complex of cisplatin with glycocholate (Bamet-R2).

摘要: Abstract The aim of this work was to investigate both the existence enterohepatic circulation cisplatin-cholylglycinate complex, Bamet-R2, and relevance biliary versus urinary excretion compound. Two experimental models were used: (i) intraluminal perfusion `in situ' ileum in anaesthetized rats bearing a catheter that permitted bile sample collection (ii) conscious which permanent intraarterial had been implanted carry out sequential blood sampling after intravenous (i.v.) or intragastric (i.g.) drug administration. Total platinum serum, bile, ileum, liver, urine feces measured by flameless atomic absorption spectroscopy. Serum concentration time curves obtained i.v. administration 1 μmol Bamet-R2 cisplatin revealed area under curve significantly higher for than (+48%). Non-ultrafiltrable accounted 54.8 48.4% serum 168 h administration, respectively. When animals received i.g. concentrations total markedly (three-fold) was, also case, (+28%). This part due enhanced intestinal as confirmed experiments on perfused rat where amount found tissue with media containing compared instead added media. Moreover, rats, kidney three-fold lower cisplatin, while elimination former compound into four-fold latter. In summary, these results indicate addition previously reported cytostatic activity complex has interesting cholephilic characteristics typical acids, such low together secretion, probably endowed cholylglycyl moiety included molecule.