paclitaxel was administered alone or with high dose tamoxifen to individuals with primary or metastatic brain tumors. The authors proposed that serum tamoxifen levels were too low to inhibit P gp in vivo. Several studies examined the role of P gp in CNS distribution of antitetroviral drugs in humans by assuming that CSF is a biomarker of drug concentrations in the mind Vortioxetine ISF. As pointed out in Section 3. 1, this assumption is fraught with problems. Khaliq et al assessed the result of ketoconazole on CSF concentrations of ritonavir or saquinavir in patients infected with HIV. Ketoconazole improved ritonavir CSF to plasma unbound focus ratio by 2. 9 fold. The increase in saquinvir CSF to plasma unbound rate was insignificant, probably as a result of small subject numbers and large interindividual variability in treatment effect. The authors suggested that inhibition of efflux transporters may be used to improve treatment of HIV in the CNS. Likewise, van Praag et al. added ritonavir to individuals treated with zidovudine or stavudine, lamivudine, abacavir, nevirapine or indinavir. Average serum trough levels of indinavir increased 5. 2 collapse, but serum peak levels remained unchanged in the existence of ritonavir, indicating decreased elimination half Infectious causes of cancer life of indinavir because of this of inhibition of its endemic approval by ritonavir. The typical indinavir CSF concentration increased from 39 ng/ml to 104 ng/ml. Ergo, when normalized by peak plasma concentration, however not by trough levels, ritonavir improved 2. 6 collapse the CSF to plasma ratio of indinavir. These results demonstrate the significance of research design when interpreting DDIs in the degree of CNS concentrations. Under steadystate conditions or when complete AUC users are characterized, changes in systemic drug concentrations should not influence the CSF to plasma or brain to plasma concentration of the drug and consequently shouldn’t confound interpretation of such data. To overcome issues related to drawing individual CSF examples, Haas et al. Acquired successive CSF and plasma samples from HIV-INFECTED patients for analysis of CSF to plasma AUC proportion. This study demonstrated that the primary mechanism for ritonavir indinavir relationship was increased plasma levels of indinavir resulting from hepatic CYP3A inhibition by ritonavir. The transporter theory in refractory epilepsy resulted in the assessment of G gp inhibitors as add on treatments to anti-epileptic drugs for treating intractable epilepsy. Two case studies describe reversal of drug resistance in patients with refractory epilepsy treated with multiple anti-convulsants by verapamil. Subsequent studies in patients with drug-resistant epilepsy substantiated the consequence of combined treatment with anti-epileptic drugs and verapamil.