Pharmacokinetics and toxicity of dexniguldipine after single and repetitive daily 4 h infusions in cancer patients

Mross, Klaus; Mayer, U.; Wörmann, Bernhard; Hanauske, Axel‐R.; Lehmann, M.; Hossfeld, Dieter K.

doi:10.1097/00001813-199409001-00104

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“…With many modulators the effective concentrations required to adequately modulate P-glycoprotein activity are significantly above the normal therapeutic dose. In the case of the calcium channel blockers, the doselimiting cardiovascular toxicity has very often made it difficult to administer doses high enough to reach serum concentrations of 6-10 mM, which are required to fully inhibit P-glycoprotein [22,80,85]. Administration of cyclosporin A might be contraindicated by its nephrotoxicity.…”

Section: How To Reverse the Mdr Phenotypementioning

confidence: 99%

The MDR phenotype in hematologic malignancies: prognostic relevance and future perspectives

Hegewisch-Becker

Hossfeld

1996

Annals of Hematology

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The multidrug resistant (MDR) phenotype has been suspected as a major cause of treatment failure in hematologic malignancies. Numerous studies have investigated the expression of the MDR1 gene product, P-glycoprotein, in leukemia, lymphoma and myeloma. Studies in myelogenous leukemia and myeloma have so far provided best evidence for a significant correlation between P-glycoprotein expression and response to chemotherapy, although large discrepancies in the proportion of positive cells limit any definite conclusion. Differences in P-glycoprotein detection techniques and methodology may account for the divergent results thus emphasizing the necessity for standardized methods of detection. Despite this, encouraging clinical results have been obtained using MDR modulators in combination with conventional chemotherapy to inhibit the activity of the P-glycoprotein pump. The paper summarizes currently available clinical data and provides guidelines for future trials aimed to reverse the MDR phenotype. The potential of idarubicin to overcome the MDR phenotype is also discussed.

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Section: How To Reverse the Mdr Phenotypementioning

confidence: 99%