Pharmacology of intracellular cytosine-arabinoside-5′-triphosphate in malignant cells of pediatric patients with initial or relapsed leukemia and in normal lymphocytes
| العنوان: | Pharmacology of intracellular cytosine-arabinoside-5′-triphosphate in malignant cells of pediatric patients with initial or relapsed leukemia and in normal lymphocytes |
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| المؤلفون: | Bernhard Kornhuber, E. Mutschler, E. Rohrbach, G. Hollatz, Dirk Schwabe, Ulrike Koehl, K. Visschedyk, J. Cinatl, Joerg Kreuter |
| المصدر: | Cancer Chemotherapy and Pharmacology. 60:467-477 |
| بيانات النشر: | Springer Science and Business Media LLC, 2006. |
| سنة النشر: | 2006 |
| مصطلحات موضوعية: | Cancer Research, Adolescent, medicine.drug_class, Lymphocyte, Pharmacology, Toxicology, Antimetabolite, Cell Line, Inhibitory Concentration 50, Pharmacokinetics, Recurrence, Cell Line, Tumor, Arabinofuranosylcytosine Triphosphate, medicine, Humans, heterocyclic compounds, Pharmacology (medical), MTT assay, Lymphocytes, Child, Chromatography, High Pressure Liquid, Acute leukemia, Chemistry, Cytarabine, Infant, Precursor Cell Lymphoblastic Leukemia-Lymphoma, medicine.disease, Leukemia, medicine.anatomical_structure, Oncology, Child, Preschool, Intracellular, Half-Life, medicine.drug |
| الوصف: | The prodrug cytosinearabinoside (ara-C) is widely used in the treatment of acute leukemias. The active drug is the intracellular metabolite cytosine-arabinoside-5′-triphosphate (ara-CTP). The purpose of the present study was to investigate the relation between sensitivity and pharmacokinetic parameters C max, t 1/2 and AUC of ara-CTP. The obtained results were compared to previous studies. C max, t 1/2 and AUC of ara-CTP were assessed in leukemic cells of 17 pediatric patients with acute lymphoblastic leukemia (ALL) and in 6 lymphoblastic cell lines and compared with normal lymphocytes of 9 healthy donors by high pressure liquid chromatography (HPLC). The sensitivity of the cells against ara-C was determined by the MTT assay. The intracellular accumulation of ara-CTP was significantly lower in normal lymphocytes (C max 47.7–60.9 pmol/106 cells) compared to leukemic cell lines (C max 11–1128 pmol/106 cells) and leukemic cells of our patients (C max 85.9–631 pmol/106 cells). Similar results were found for the AUC. There was no significant difference between initial and relapsed leukemias in our small cohort. A correlation between sensitivity in terms of IC50 values and the intracellular ara-CTP accumulation was observed in cell lines, but not in leukemic cells and normal lymphocytes from healthy donors. Pharmacokinetic parameters varied tremendously in leukemic cells in contrast to normal lymphocytes without a difference in sensitivity. It is worthwhile to compare literature data to assess an optimal dosage of ara-C in pediatric patients. |
| تدمد: | 1432-0843 0344-5704 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::942b70e221dd1fa26891c2a263d17f64 https://doi.org/10.1007/s00280-006-0386-3 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....942b70e221dd1fa26891c2a263d17f64 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 14320843 03445704 |
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