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• W1941252177 endingPage "1844" @default.
• W1941252177 startingPage "1837" @default.
• W1941252177 abstract "PURPOSE: The aim of the present study was to evaluate the effect of the cyclosporine derivative valspodar (PSC 833; Amdray, Novartis Pharma, Basel, Switzerland) on the concentration of daunorubicin (dnr) in leukemic blast cells in vivo during treatment. PATIENTS AND METHODS: Ten patients with acute myeloid leukemia (AML) were included. Leukemic cells from seven of the patients were P-glycoprotein (Pgp)–positive. dnr 100 mg/m 2 was given as a continuous infusion over 72 hours. After 24 hours, a loading dose of valspodar was given, followed by a 36-hour infusion of 10 mg/kg per 24 hours. Blood samples were drawn at regular intervals, and concentrations of dnr and its main metabolite, daunorubicinol, in plasma and isolated leukemic cells were determined by high-pressure liquid chromatography. RESULTS: The mean dnr concentrations in leukemic cells 24 hours after the start of infusion (before valspodar) were 18.8 μmol/L in Pgp-negative samples and 13.5 μmol/L in Pgp-positive samples. After 8 hours of valspodar infusion, these values were 25.8 and 24.0 μmol/L, respectively. The effect of valspodar was evaluated from the ratio of the area under the curve (AUC) for dnr concentration versus time in leukemic cells to the AUC for dnr concentration against time in the plasma. For the seven patients with Pgp-positive leukemia, the mean ratio increased by 52%, from 545 on day 1 to 830 on day 2 (P < .05) when valspodar was given. In the three patients with Pgp-negative leukemia, no significant difference was observed. CONCLUSION: These results strongly suggest that valspodar, by interacting with Pgp, can increase the cellular uptake of dnr in leukemic blasts in vivo." @default.
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• W1941252177 date "2000-05-09" @default.
• W1941252177 modified "2023-10-10" @default.
• W1941252177 title "P-Glycoprotein Inhibitor Valspodar (PSC 833) Increases the Intracellular Concentrations of Daunorubicin In Vivo in Patients With P-Glycoprotein–Positive Acute Myeloid Leukemia" @default.
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• W1941252177 doi "https://doi.org/10.1200/jco.2000.18.9.1837" @default.
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