de VrieItinib sorafenib absorption and brain, and de Vries ENMD-2076 et al. ver ffentlichten similar results for topotecan. Thus, in pr Clinical trials erh Hte elacridar fa It significant brain penetration of drugs that are P gp dual BCRP substrates. Apart from these compounds, which have been developed for use as agents to reverse multiple drug resistance, several studies drugs that two P gp BCRP substrates were competitively inhibit both Tr hunter is. That’m Ren various anti-tyrosine kinase inhibitors has been shown to be substrates for both P gp and BCRP. In vitro studies have shown that tyrosine kinase inhibitors such as erlotinib, gefitinib, lapatinib and sunitinib ABC transporters, especially inhibits P gp and BCRP and beat the m Improve Possible use of these agents in combination therapy pharmacokinetics of drugs.
In 2006, Zhuang et al. showed that the co-administration of gefitinib leads to a significant Erh increase the brain penetration of topotecan. The same group showed that gefitinib and intracellular Re tumor exposure to topotecan in a mouse model of glioma increased Ht. In a recent clinical study using Furman and his colleagues inhibit Cilomilast intestinal P gp and BCRP and gefitinib has been shown to increased the oral bioavailability of irinotecan hen. An interesting study by Nakanishi et al. in 2006 showed that imatinib resistance reduced BCRP expression BCRP l mediates between. The mechanism behind these different reactions in downstream effects of imatinib, which went to the phosphorylation of Akt, then what expression to reduced BCRP.
Many tyrosine kinase inhibitors have an inhibitory effect on the k PI3K Pathway PTEN signaling These drugs act Can therefore reduce the functional activity of t and protein expression of ABC transporters, in particular by blocking the PI3K Akt signaling BCRP. Combination of tyrosine kinase inhibitors with other anticancer drugs may therefore have a bimodal effect of ABC transporters in which the transporter expression can be entered decreased function associated with competitive inhibition Dinner drug penetration increased fa it well above the BBB and drug concentrations potentially a significant increase in brain tumors. In conclusion, the simultaneous dual inhibitors BCRP P gp can therefore improve the delivery and efficacy of drugs that are substrates of the central nervous system.
Recent data indicate that to inhibit the use of tyrosine kinase inhibitors for the P gp BCRP k Nnten have many advantages, particularly when the anti-cancer agent improves the supply of its own. To the brain 5 The blood-brain barrier in brain tumors Recent studies show that the integrity of t The BBB in brain tumors found Hrdet is questioning their r Limitation in the delivery of chemotherapeutic agents to brain tumors. In fact, reports show that the concentrations of anticancer drugs in tumor tissue resected remarkably high. In this regard, Pitz et al. lt contains a summary of the concentrations of anticancer drugs to brain tumors, and showed that high concentrations of active ingredients in the field of tumor-enrichment. Hofer and colleagues