N between tipifarnib and total and unbound cisplatin was observed in this WYE-354 study. This result was expected, as cisplatin Haupts chlich excreted by the kidneys and was not catalyzed enzymatic metabolism. No significant difference in the level of DNA adducts was found in the presence or absence of Tipifarnib. This was also expected since the concentrations of cisplatin with or without tipifarnib showed no difference. There was no interaction between the drug and gemcitabine and tipifarnib dFdCTP. This is consistent with the data from the previous test Patnaik et al, but in our study, a significant difference was found between tipifarnib and dFdU.
Gemcitabine is metabolized to its active metabolite by deoxycytidine dFdCTP and can by deoxycytidine deaminase dFdU, w W During the tipifarnib glucuronidation and oxidation by cytochrome P chlich main tipifarnib plasma proteins bound Janssen Research Foundation, w If enabled binding to plasma proteins Gemcitabine ssigbar Shipley et al, it is unlikely that the inhibition of metabolism PD184352 of any drug or the movement of plasma proteins m Possible mechanisms of pharmacokinetic interactions. In vitro studies are warranted aufzukl the mechanism of interaction between tipifarnib and dFdU Ren. It is expected that the interaction size E little or no clinical consequences. The pharmacokinetics of tipifarnib were not significantly changed by co-administration of gemcitabine and cisplatin ver.
There was a big e interindividual variability Tet pharmacokinetics of tipifarnib, which was observed in the Phase I monotherapy and Zujewski Karp et al et al et al Crul This study showed that tipifarnib sr in combination with gemcitabine and cisplatin and s important and clinically significant drug interactions are not apparent. In accordance with this conclusion is the gegenw Rtige regime evidence activity t-t in a variety of tumors. There were eight partial remission best Foundation and the patient remained stable for more than a few weeks. As this study is a combination of tipifarnib with cytotoxic therapy is effective, it must be documented efficacy of the promising results of this study be interpreted with caution. Nevertheless, phase II studies of this association are guaranteed in a number of solid tumors.
It is interesting to determine whether this combination green or equal to a standard treatment of gemcitabine and cisplatin alone and further information on the mechanism of action of tipifarnib k surrogate w Choose k Can auszuw necessary to determine if the recommended dose is also effective . Tipifarnib R Zarnestra ? is a potent and selective inhibitor of the enzyme farnesyl competition FTase. This enzyme is in the processing and the activation of signaling molecules with cell proliferation and malignant transformation, such as Ras, Rho B, lamin and Rac proteins associated important. FTase inhibition by tipifarnib induced antileuk endemic tumor has demonstrated both in vitro and in vivo in animal models. The cell type and tissue responses induced tumors Ren tipifarnib treatment