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Metabolism, transport and anticancer effect of classical and novel taxanes
Václavíková, Radka ; Gut, Ivan (vedoucí práce) ; Perlík, František (oponent) ; Anzenbacherová, Eva (oponent)
L I I I I I I I I t CONCLUSIONS The dissertation thesis contributes to detail knowledge of the metabolism, transport and anticancer effects of classical taxanes (paclitaxel and docetaxel) as well as their novel synthetic analogs (SB-T-1103, SB-1'-1214 and SB-T-1216). The r]lost rmportanl reslrlts concerning studies on these anticancet drugs are srultnarized as iollorvs: o Detail metabolisrrr oť paclitaxel and docetaxel rvas estimated in human. rat. pig arrd minipig liver microsomes. The metabolism of docetaxel rvas the same i:r all four tested species. Drug rvas metabolized mainly to hydroxydocetaxel and two minor h1'droxyoxazol.idinones A and B. Despite various simiiarities between human and pig netabolism of paclitaxel, the profile oť paclitaxel metabolites in the studied species r'u.as different and main hunan metabolite óo.oHP renrains uniquelv human one' The other new metabolites of paclitaxel w.ere revealed. speciíicall1 di-oHP in ra1s and a new. hydroxypaclitaxel in rats. pigs and minipigs. q,here thrs metabolite is the main metabolic pathway oť paciitaxel. The major enzymes responsible for oxidative metaboiism of paclitaxei are CYP2CB and CYP3A4 in humans and CYP3Ai/2 in rats. Docelaxel is oxidatively metabolized by GYP3A famil"v in humans as rvell as in rats. The oxidation metabolism of classical...
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