Kinetics and sensitivity of daunorubicin in patients with acute leukemia
Leukemia cells isolated from eight patients with acute leukemia before treatment were examined for in vitro uptake of daunorubicin (DNR) and inhibition of DNA synthesis. In addition, plasma and cellular levels of DNR and daunorubicinol (DOL) were examined in six of the eight patients. Inhibition of...
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| Veröffentlicht in: | Cancer chemotherapy and pharmacology 1984-01, Vol.13 (3), p.230-234 |
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| creator | DE GREGORIO, M. W HOLLERAN, W. M MACHER, B. A LINKER, C. A WILBUR, J. R |
| description | Leukemia cells isolated from eight patients with acute leukemia before treatment were examined for in vitro uptake of daunorubicin (DNR) and inhibition of DNA synthesis. In addition, plasma and cellular levels of DNR and daunorubicinol (DOL) were examined in six of the eight patients. Inhibition of DNA synthesis was determined with a 3H-thymidine incorporation assay. In vitro cellular 14C-DNR was quantified by means of liquid scintillation spectrometry, whereas in vivo DNR and DOL concentrations were determined by high-performance liquid chromatography. In vitro intracellular plateau concentrations of DNR were achieved within 1-2 h after continuous exposure to 0.01, 0.1, and 1.0 microgram/ml in the majority of cases. Based on our in vitro studies, a dose-response curve was found between increasing intracellular DNR and incorporation of 3H-thymidine. Peak intracellular levels of DNR after treatment occurred immediately after administration of the drug, whereas intracellular DOL levels accumulated over several hours. Plasma concentrations of DNR and DOL were not useful in estimating target tissue concentrations or inhibition of 3H-thymidine incorporation. Extrapolation of in vivo cellular DNR concentrations to the in vitro dose-response curve allows an estimate of DNR sensitivity. |
| doi_str_mv | 10.1007/BF00269036 |
| format | Article |
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W ; HOLLERAN, W. M ; MACHER, B. A ; LINKER, C. A ; WILBUR, J. R</creator><creatorcontrib>DE GREGORIO, M. W ; HOLLERAN, W. M ; MACHER, B. A ; LINKER, C. A ; WILBUR, J. R</creatorcontrib><description>Leukemia cells isolated from eight patients with acute leukemia before treatment were examined for in vitro uptake of daunorubicin (DNR) and inhibition of DNA synthesis. In addition, plasma and cellular levels of DNR and daunorubicinol (DOL) were examined in six of the eight patients. Inhibition of DNA synthesis was determined with a 3H-thymidine incorporation assay. In vitro cellular 14C-DNR was quantified by means of liquid scintillation spectrometry, whereas in vivo DNR and DOL concentrations were determined by high-performance liquid chromatography. In vitro intracellular plateau concentrations of DNR were achieved within 1-2 h after continuous exposure to 0.01, 0.1, and 1.0 microgram/ml in the majority of cases. Based on our in vitro studies, a dose-response curve was found between increasing intracellular DNR and incorporation of 3H-thymidine. Peak intracellular levels of DNR after treatment occurred immediately after administration of the drug, whereas intracellular DOL levels accumulated over several hours. Plasma concentrations of DNR and DOL were not useful in estimating target tissue concentrations or inhibition of 3H-thymidine incorporation. Extrapolation of in vivo cellular DNR concentrations to the in vitro dose-response curve allows an estimate of DNR sensitivity.</description><identifier>ISSN: 0344-5704</identifier><identifier>EISSN: 1432-0843</identifier><identifier>DOI: 10.1007/BF00269036</identifier><identifier>PMID: 6488444</identifier><identifier>CODEN: CCPHDZ</identifier><language>eng</language><publisher>Berlin: Springer</publisher><subject>Adolescent ; Adult ; Aged ; Antineoplastic agents ; Biological and medical sciences ; Biological Transport ; Cells, Cultured ; Chemotherapy ; Daunorubicin - analogs & derivatives ; Daunorubicin - metabolism ; DNA Replication - drug effects ; DNA, Neoplasm - biosynthesis ; Female ; Humans ; Leukemia - drug therapy ; Male ; Medical sciences ; Middle Aged ; Pharmacology. 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W</creatorcontrib><creatorcontrib>HOLLERAN, W. M</creatorcontrib><creatorcontrib>MACHER, B. A</creatorcontrib><creatorcontrib>LINKER, C. A</creatorcontrib><creatorcontrib>WILBUR, J. R</creatorcontrib><title>Kinetics and sensitivity of daunorubicin in patients with acute leukemia</title><title>Cancer chemotherapy and pharmacology</title><addtitle>Cancer Chemother Pharmacol</addtitle><description>Leukemia cells isolated from eight patients with acute leukemia before treatment were examined for in vitro uptake of daunorubicin (DNR) and inhibition of DNA synthesis. In addition, plasma and cellular levels of DNR and daunorubicinol (DOL) were examined in six of the eight patients. Inhibition of DNA synthesis was determined with a 3H-thymidine incorporation assay. In vitro cellular 14C-DNR was quantified by means of liquid scintillation spectrometry, whereas in vivo DNR and DOL concentrations were determined by high-performance liquid chromatography. In vitro intracellular plateau concentrations of DNR were achieved within 1-2 h after continuous exposure to 0.01, 0.1, and 1.0 microgram/ml in the majority of cases. Based on our in vitro studies, a dose-response curve was found between increasing intracellular DNR and incorporation of 3H-thymidine. Peak intracellular levels of DNR after treatment occurred immediately after administration of the drug, whereas intracellular DOL levels accumulated over several hours. Plasma concentrations of DNR and DOL were not useful in estimating target tissue concentrations or inhibition of 3H-thymidine incorporation. Extrapolation of in vivo cellular DNR concentrations to the in vitro dose-response curve allows an estimate of DNR sensitivity.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Biological Transport</subject><subject>Cells, Cultured</subject><subject>Chemotherapy</subject><subject>Daunorubicin - analogs & derivatives</subject><subject>Daunorubicin - metabolism</subject><subject>DNA Replication - drug effects</subject><subject>DNA, Neoplasm - biosynthesis</subject><subject>Female</subject><subject>Humans</subject><subject>Leukemia - drug therapy</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Pharmacology. 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W</creatorcontrib><creatorcontrib>HOLLERAN, W. M</creatorcontrib><creatorcontrib>MACHER, B. A</creatorcontrib><creatorcontrib>LINKER, C. A</creatorcontrib><creatorcontrib>WILBUR, J. R</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Cancer chemotherapy and pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>DE GREGORIO, M. W</au><au>HOLLERAN, W. M</au><au>MACHER, B. A</au><au>LINKER, C. A</au><au>WILBUR, J. R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Kinetics and sensitivity of daunorubicin in patients with acute leukemia</atitle><jtitle>Cancer chemotherapy and pharmacology</jtitle><addtitle>Cancer Chemother Pharmacol</addtitle><date>1984-01-01</date><risdate>1984</risdate><volume>13</volume><issue>3</issue><spage>230</spage><epage>234</epage><pages>230-234</pages><issn>0344-5704</issn><eissn>1432-0843</eissn><coden>CCPHDZ</coden><abstract>Leukemia cells isolated from eight patients with acute leukemia before treatment were examined for in vitro uptake of daunorubicin (DNR) and inhibition of DNA synthesis. In addition, plasma and cellular levels of DNR and daunorubicinol (DOL) were examined in six of the eight patients. Inhibition of DNA synthesis was determined with a 3H-thymidine incorporation assay. In vitro cellular 14C-DNR was quantified by means of liquid scintillation spectrometry, whereas in vivo DNR and DOL concentrations were determined by high-performance liquid chromatography. In vitro intracellular plateau concentrations of DNR were achieved within 1-2 h after continuous exposure to 0.01, 0.1, and 1.0 microgram/ml in the majority of cases. Based on our in vitro studies, a dose-response curve was found between increasing intracellular DNR and incorporation of 3H-thymidine. Peak intracellular levels of DNR after treatment occurred immediately after administration of the drug, whereas intracellular DOL levels accumulated over several hours. Plasma concentrations of DNR and DOL were not useful in estimating target tissue concentrations or inhibition of 3H-thymidine incorporation. Extrapolation of in vivo cellular DNR concentrations to the in vitro dose-response curve allows an estimate of DNR sensitivity.</abstract><cop>Berlin</cop><pub>Springer</pub><pmid>6488444</pmid><doi>10.1007/BF00269036</doi><tpages>5</tpages></addata></record> |
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| ispartof | Cancer chemotherapy and pharmacology, 1984-01, Vol.13 (3), p.230-234 |
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| language | eng |
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| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | Adolescent Adult Aged Antineoplastic agents Biological and medical sciences Biological Transport Cells, Cultured Chemotherapy Daunorubicin - analogs & derivatives Daunorubicin - metabolism DNA Replication - drug effects DNA, Neoplasm - biosynthesis Female Humans Leukemia - drug therapy Male Medical sciences Middle Aged Pharmacology. Drug treatments |
| title | Kinetics and sensitivity of daunorubicin in patients with acute leukemia |
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