Kutasevych N. Pharmacokinetics of calix[4]arene derivatives

Pharmacokinetic parameters of new class compounds – calix[4]aren derivatives – were defined with the help of computer modeling and experimental researches. Proper isoforms CYP450, which catalyze hydroxylation reactions (1A2, 2C9, 2C19, 2D6 and 3A4) due to the presence of metaboform areas, are determined. The metabolism process was established experimentally. The structure of metabolite calix[4]aren was defined with radiochromatography and mass-spectrometry methods. The obtained results testify to the selective binding with K+ cations. It is established that the main way of elimination is excretion of calix[4]aren with feces. The mechanism of calix[4]aren derivatives absorption consists in mechanic evacuation from the stomach, passive absorption in the upper departments of the thin bowel and coming to the lymphatic system, which is confi rmed with the help of biomarker – 4-3H-difenil. It is established experimentally that calix[4]arens are not toxic (LD>2000 mg/kg) with per oral and intraabdominal administration. So, we can make a conclusion that calix[4]arens are practically nontoxic (VI class of toxicity).