Evaluation of loperamide disposition in rats unveiled that t

Examination of loperamide personality in mice unveiled 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 into the head, without a change in its CSF to blood concentration ratio. These data claim that CSF concentration as a surrogate marker for brain drug concentration ought to be used with caution, specially to assess drug interactions natural product library at the BBB. Moreover, 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. Applied PET to investigate 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 very low and seemed unchanged after the administration of the inhibitor. Though Choo et al have previously demonstrated in rats that G gp at the BBB is more resistant to inhibition by tariquidar than in other cells, when loperamide was employed as the substrate, the reason for this tissue specificity of the interaction is unknown. This finding can also be as opposed to the 4. 3 fold increase in paclitaxel head uptake when it had been co used Immune system with tariquidar to mice. As opposed to the wealth of information on G gp inhibition, not as is known about the effect of Pgp induction at the BBB. In one of the earlier studies, subjects were treated with morphine or dexamethasone for 5 days. Both substances ubiquitin conjugating decreased the effect of morphine and enhanced G glycoprotein expression in the brain, compared to those observed in animals treated with the vehicle. The researchers postulated that enhanced brain G gp activity following chronic contact with morphine or dexamethasone might have caused the lower brain levels of the drug. Chronic exposure of rat brain endothelial cells to other drugs, including phenobarbital, phenytoin and carbamazepine can also cause induction of P gp expression and functionality in vitro and in vivo. Similarly, HIV protease inhibitors have been proven to up regulate P gp expression in vitro in a mind endothelial cell line. Studies about activity and expression of transcription factors that regulate the BBB expression of G gp and other transporters are conflicting. Bauer and colleagues provided proof 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.

Evaluation of loperamide disposition in rats unveiled that t