Analysis of loperamide personality in rats unveiled that the influence of P gp inhibition on brain uptake of loperamide was blunted by non P gp substrate radioactive metabolites of loperamide. Zosuquidar somewhat increased the distribution of nelfinavir in to the head, without a change in its CSF to blood concentration ratio. These data suggest that CSF concentration as a surrogate marker for brain drug concentration ought to be used in combination with caution, specially to evaluate drug interactions Icotinib at the BBB. Likewise, doxorubicin CSF concentrations in four adult rhesus monkeys were below the limit of detection if the drug was used alone or in combination with intravenous cyclosporine. Kurdziel et al. utilized PET to asses the tissue distribution of paclitaxel in the absence and the presence of tariquidar in 3 rhesus monkeys. Despite improvements in the distribution of radioactivity into liver, lung, and kidney with tariquidar administration, paclitaxel uptake into the brain was really low and seemed unchanged after the administration of the inhibitor. The reason behind this tissue specificity of the relationship is unknown, though Choo et al have previously demonstrated in rats that P gp at the BBB is more resistant to inhibition by tariquidar than in other areas, when loperamide was used as the substrate. This finding is also as opposed to the 4. 3 fold increase in paclitaxel brain uptake when it had been company given Gene expression with tariquidar to rats. Contrary to the wealth of data on G gp inhibition, much less is known about the influence of Pgp induction at the BBB. In one of the earlier studies, rats were handled with morphine or dexamethasone for 5 days. Both compounds buy Everolimus decreased the effect of morphine and improved G glycoprotein expression in the mind, in comparison to those noticed in animals treated with the vehicle. The investigators postulated that improved brain G gp activity following chronic experience of morphine or dexamethasone may have induced the lower brain concentrations of the drug. Chronic exposure of rat brain endothelial cells to other medications, including phenobarbital, phenytoin and carbamazepine may also cause induction of P gp expression and functionality in vitro and in vivo. Likewise, HIV protease inhibitors have demonstrated an ability to up regulate P gp expression in vitro in a human brain endothelial cell line. Studies about expression and activity of transcription factors that regulate the BBB expression of other transporters and P gp are contradictory. Bauer and colleagues provided proof that the nuclear receptor pregnane X receptor is present in rat brain capillaries, where it can potentially mediate DDIs. Upon activation by dexamethasone, PXR regulates the expression of P gp in rat brain capillaries in vitro and in vivo.