of BCRP in brain endothelial cells changes the langj-old believes that PGP is the only NPI-2358 Plinabulin carrier for the efflux of drugs important to the Pr BUREAU. However, BCRP expression in the BBB has not clearly correlated with low brain penetration of all substrates, BCRP. For example, Lee et al. using in situ brain perfusion studies dehydroepiandrosterone and BCRP substrates mitoxantrone and noted that brain penetration of both compounds not in M usen BCRP1 erh ht. If milarly, Giri and colleagues showed that. BCRP efflux of antiretroviral drugs abacavir and zidovudine in vitro However, despite the absence of the brain uptake of these compounds BCRP has not lifted in BCRP1 mouse. One conclusion from these studies is that the BCRP has played an r Minderj-old Efflux in the BBB and another study showed that.
Interactions with substrates of BCRP in vitro rarely visible effects of the BBB in vivo In contrast, other studies have shown the activity of t Demonstrates transport of BCRP Office. Cisternino and colleagues have shown that. BCRP limits prazosin and mitoxantrone, two prototypes of BCRP substrates in the brain Similar Enokizono Tipifarnib et al. and Breedveld et al. shown that the distribution of drugs in the brain increased significantly ht in BCRP1 mouse. We have also recently reported that sorafenib transport in the brain was significantly at M Usen BCRP1 erh Ht. Taken together, the contradictory results of BCRP mediated efflux triggered by the brain St a controversy over the r Airline that the BBB lead to new studies.
With the development of the knockout mouse BCRP P gp BCRP1 researchers were able to study the combined effect of these efflux transporters in drug delivery across the BBB. de Vries et al. showed that usen brain uptake of topotecan, a substrate for both P gp and BCRP, not in M, which the BCRP increased ht. Mice P gp knockout brain topotecan concentration increased Hte slightly by a factor of 1.5. In contrast, M Usen both P gp and BCRP BCRP1, brain uptake of topotecan increased more than 12-fold Ht. Thus the absence of the two P gp and BCRP has entered Born an effect much gr It as the combined effects of individual knock-M Usen Tr was hunter. This finding was. By Polli et al Lapatinib in gp knockout M nozzles P BCRP. We have shown the same thing with dasatinib, gefitinib and sorafenib.
Although these drugs are substrates for both P gp and BCRP, the lack of a carrier Ger not increased significantly Hen the supply of each drug on the brain, but the gr Te improve the brain penetration has been observed when the Tr two hunters absent or inhibited the BBB. Several studies have now shown that this is also for other dual P gp and BCRP substrates as well. Figure 1 summarizes the latest data of Kawamura et al. the show this phenomenon Ph. These results suggest that the inhibitory