Assessment of loperamide temperament in mice revealed that the effect of P gp inhibition on brain uptake of loperamide was blunted by low G gp substrate radioactive metabolites of loperamide. Zosuquidar significantly improved the distribution of nelfinavir 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 should be used in combination with caution, specially to determine drug interactions CTEP in the BBB. Likewise, doxorubicin CSF concentrations in four adult rhesus monkeys were below the limit of detection if the drug was administered alone or in combination with intravenous cyclosporine. Kurdziel et al. Employed PET to test the tissue distribution of paclitaxel in the absence and the presence of tariquidar in 3 rhesus monkeys. Despite changes in the distribution of radioactivity into liver, lung, and kidney with tariquidar administration, paclitaxel uptake into the head was really low and appeared unchanged after the administration of the chemical. Although 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, the reason behind this tissue specificity of the relationship is unknown. This finding can also be contrary to the 4. 3 fold increase in paclitaxel brain uptake when it had been company applied Urogenital pelvic malignancy with tariquidar to mice. In contrast to the wealth of information on G gp inhibition, much less is known about the effect of Pgp induction in the BBB. In one of the earlier in the day studies, subjects were treated with morphine or dexamethasone for 5 days. Both compounds MAPK phosphorylation decreased the antinociceptive effect of morphine and enhanced P glycoprotein expression in the mind, in comparison to those observed in animals treated with the vehicle. The researchers postulated that improved brain P gp activity following chronic exposure to morphine or dexamethasone could have caused the lower brain levels of the drug. Chronic exposure of rat brain endothelial cells to other medications, including phenobarbital, phenytoin and carbamazepine may also lead to induction of P gp expression and functionality in vitro and in vivo. Also, HIV protease inhibitors have been shown to up regulate G gp expression in vitro in a mind endothelial cell line. Studies about expression and activity of transcription factors that regulate the BBB expression of G gp and other transporters are conflicting. Bauer and colleagues presented evidence that the nuclear receptor pregnane X receptor exists 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.