It has been widely assumed that the influence of DDIs at the human BBB will be as large as those noticed in animals. However, regardless of the clinical significance of DDIs at blood-brain interfaces, due to technical buy AG-1478 and moral limits, so far only a few studies have addressed this problem in humans. 3To assess the CNS distribution of cyclophosphamide and ifosfamide, Yule et al evaluated the CSF and plasma levels of these drugs in 25 pediatric oncology patients. Topics received cyclophosphamide or constant infusion of ifosfamide over 72 hours. 7 Patients who were treated with cyclophosphamide for non Hodgkins lymphoma had significantly higher cyclophosphamide CSF concentrations, compared with 13 patients that were treated for severe lynphoblastic leukemia. The CSF toplasma concentration ratio of cyclophosphamide was 3 fold greater in lymphoma than in leukemia patients. The authors suggested that the differences could result from tightening of the BBB by co administration of dexamethasone for the treatment of acute lymphoblastic leukemia. Equally, one patient that gotten dexamethasone had the best CSF to plasma concentration ratio of ifosfamide. It could lead to DDIs with respect to drug distribution into the CNS, since dexamethasone reduces BBB permeability by multiple mechanisms. The clinical importance of this process of DDI is not clear. 3CSF concentrations have also been utilized to assess the effect of osmotic BBBD on CNS penetration of methotrexate. For example, intra arterial administration of methotrexate with osmotic BBBD led to up to 6 fold development of methotrexate CSF transmission, compared to intravenous or intra arterially administration. Generally, osmotic BBBD improved clinical results of cancer chemotherapy in phase II studies and phase I, but hasn’t been considered in larger clinical trials. Currently, issues continue to exist regarding efficacy and toxicity of osmotic BBBD. First, although osmotic BBBD possibly increases the distribution of hydrophilic compounds into Cathepsin Inhibitor 1 the ISF, it could not boost their distribution into the tumor itself, given the abnormalities of tumor microvessels. Next, non-specific BBB disruption can augment neurotoxicity of the chemotherapeutic materials along with that of several other elements that normally wouldn’t gain access into brain parenchyma. More selective opening of tumefaction blood barrier using bradykinin analogues has been analyzed in pediatric patients with brain tumors, but didn’t improve the efficacy of carboplatin in these patients. Currently, medical studies on BBBD to improve CNS drug delivery are continuing, but the usage of this process is restricted to a couple centers and this kind of DDI isn’t anticipated to occur with using conventional therapeutic regimens.