Pharmacokinetic/pharmacodynamic correlation and blood-level testing in imatinib therapy for chronic myeloid leukemia
Imatinib is the current standard of care in the treatment of chronic myeloid leukemia (CML), inducing durable responses and prolonged progression-free survival. However, plasma exposure to the drug from a given dosing regimen can vary widely among patients. Reasons for this may include incomplete ad...
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| Veröffentlicht in: | Leukemia 2009-09, Vol.23 (9), p.1537-1544 |
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| description | Imatinib is the current standard of care in the treatment of chronic myeloid leukemia (CML), inducing durable responses and prolonged progression-free survival. However, plasma exposure to the drug from a given dosing regimen can vary widely among patients. Reasons for this may include incomplete adherence, intrinsic variations in the metabolism of imatinib, and drug–drug interactions. Data from two recent studies have shown a correlation between imatinib trough plasma concentration and clinical response, leading to suggestions that maintaining imatinib blood concentrations above ∼1000 ng/ml might be associated with improved outcomes. In patients who do not respond as well as expected to initial imatinib treatment, measurement of trough plasma concentration could assist with decisions about whether to increase the dose. Blood-level testing may also be helpful in other clinical scenarios: for example, when poor adherence is suspected, adverse reactions are unusually severe, or there is a possible drug–drug interaction. Further work is required to confirm prospectively the link between imatinib plasma concentrations and response, and to define effective trough concentrations in different patient populations. However, based on the current data, imatinib blood-level testing seems to be a useful aid when making clinical decisions in CML. |
| doi_str_mv | 10.1038/leu.2009.88 |
| format | Article |
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However, plasma exposure to the drug from a given dosing regimen can vary widely among patients. Reasons for this may include incomplete adherence, intrinsic variations in the metabolism of imatinib, and drug–drug interactions. Data from two recent studies have shown a correlation between imatinib trough plasma concentration and clinical response, leading to suggestions that maintaining imatinib blood concentrations above ∼1000 ng/ml might be associated with improved outcomes. In patients who do not respond as well as expected to initial imatinib treatment, measurement of trough plasma concentration could assist with decisions about whether to increase the dose. Blood-level testing may also be helpful in other clinical scenarios: for example, when poor adherence is suspected, adverse reactions are unusually severe, or there is a possible drug–drug interaction. Further work is required to confirm prospectively the link between imatinib plasma concentrations and response, and to define effective trough concentrations in different patient populations. However, based on the current data, imatinib blood-level testing seems to be a useful aid when making clinical decisions in CML.</description><identifier>ISSN: 0887-6924</identifier><identifier>EISSN: 1476-5551</identifier><identifier>DOI: 10.1038/leu.2009.88</identifier><identifier>PMID: 19404318</identifier><identifier>CODEN: LEUKED</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Antineoplastic Agents - therapeutic use ; Benzamides ; Biological and medical sciences ; Blood ; Cancer ; Cancer Research ; Chronic myeloid leukemia ; Critical Care Medicine ; Decisions ; Diagnosis ; Dosage ; Drug dosages ; Drug interaction ; Drug Interactions ; Drug metabolism ; Drug therapy ; Hematologic and hematopoietic diseases ; Hematology ; Humans ; Imatinib ; Imatinib Mesylate ; Inhibitor drugs ; Intensive ; Internal Medicine ; Intestinal Absorption ; Kinases ; Leukemia ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Medical sciences ; Medication Adherence ; Medicine ; Medicine & Public Health ; Myeloid leukemia ; Oncology ; Orosomucoid - metabolism ; Patients ; Pharmacodynamics ; Pharmacokinetics ; Pharmacology ; Piperazines - adverse effects ; Piperazines - pharmacokinetics ; Piperazines - therapeutic use ; Plasma ; Protein Binding ; Proteins ; Pyrimidines - adverse effects ; Pyrimidines - pharmacokinetics ; Pyrimidines - therapeutic use ; review ; Targeted cancer therapy ; Treatment Failure</subject><ispartof>Leukemia, 2009-09, Vol.23 (9), p.1537-1544</ispartof><rights>Macmillan Publishers Limited 2009</rights><rights>2009 INIST-CNRS</rights><rights>COPYRIGHT 2009 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Sep 2009</rights><rights>Macmillan Publishers Limited 2009.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c641t-5d3a8bcb61b7b2ccba825ca10ee745381a9f4f1a22a9d8e4a9ccee7bf39a9bee3</citedby><cites>FETCH-LOGICAL-c641t-5d3a8bcb61b7b2ccba825ca10ee745381a9f4f1a22a9d8e4a9ccee7bf39a9bee3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/leu.2009.88$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/leu.2009.88$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21929261$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19404318$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cortes, J E</creatorcontrib><creatorcontrib>Egorin, M J</creatorcontrib><creatorcontrib>Guilhot, F</creatorcontrib><creatorcontrib>Molimard, M</creatorcontrib><creatorcontrib>Mahon, F-X</creatorcontrib><title>Pharmacokinetic/pharmacodynamic correlation and blood-level testing in imatinib therapy for chronic myeloid leukemia</title><title>Leukemia</title><addtitle>Leukemia</addtitle><addtitle>Leukemia</addtitle><description>Imatinib is the current standard of care in the treatment of chronic myeloid leukemia (CML), inducing durable responses and prolonged progression-free survival. However, plasma exposure to the drug from a given dosing regimen can vary widely among patients. Reasons for this may include incomplete adherence, intrinsic variations in the metabolism of imatinib, and drug–drug interactions. Data from two recent studies have shown a correlation between imatinib trough plasma concentration and clinical response, leading to suggestions that maintaining imatinib blood concentrations above ∼1000 ng/ml might be associated with improved outcomes. In patients who do not respond as well as expected to initial imatinib treatment, measurement of trough plasma concentration could assist with decisions about whether to increase the dose. Blood-level testing may also be helpful in other clinical scenarios: for example, when poor adherence is suspected, adverse reactions are unusually severe, or there is a possible drug–drug interaction. Further work is required to confirm prospectively the link between imatinib plasma concentrations and response, and to define effective trough concentrations in different patient populations. However, based on the current data, imatinib blood-level testing seems to be a useful aid when making clinical decisions in CML.</description><subject>Antineoplastic Agents - therapeutic use</subject><subject>Benzamides</subject><subject>Biological and medical sciences</subject><subject>Blood</subject><subject>Cancer</subject><subject>Cancer Research</subject><subject>Chronic myeloid leukemia</subject><subject>Critical Care Medicine</subject><subject>Decisions</subject><subject>Diagnosis</subject><subject>Dosage</subject><subject>Drug dosages</subject><subject>Drug interaction</subject><subject>Drug Interactions</subject><subject>Drug metabolism</subject><subject>Drug therapy</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Hematology</subject><subject>Humans</subject><subject>Imatinib</subject><subject>Imatinib Mesylate</subject><subject>Inhibitor drugs</subject><subject>Intensive</subject><subject>Internal Medicine</subject><subject>Intestinal Absorption</subject><subject>Kinases</subject><subject>Leukemia</subject><subject>Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy</subject><subject>Leukemias. 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However, plasma exposure to the drug from a given dosing regimen can vary widely among patients. Reasons for this may include incomplete adherence, intrinsic variations in the metabolism of imatinib, and drug–drug interactions. Data from two recent studies have shown a correlation between imatinib trough plasma concentration and clinical response, leading to suggestions that maintaining imatinib blood concentrations above ∼1000 ng/ml might be associated with improved outcomes. In patients who do not respond as well as expected to initial imatinib treatment, measurement of trough plasma concentration could assist with decisions about whether to increase the dose. Blood-level testing may also be helpful in other clinical scenarios: for example, when poor adherence is suspected, adverse reactions are unusually severe, or there is a possible drug–drug interaction. Further work is required to confirm prospectively the link between imatinib plasma concentrations and response, and to define effective trough concentrations in different patient populations. However, based on the current data, imatinib blood-level testing seems to be a useful aid when making clinical decisions in CML.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>19404318</pmid><doi>10.1038/leu.2009.88</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Antineoplastic Agents - therapeutic use Benzamides Biological and medical sciences Blood Cancer Cancer Research Chronic myeloid leukemia Critical Care Medicine Decisions Diagnosis Dosage Drug dosages Drug interaction Drug Interactions Drug metabolism Drug therapy Hematologic and hematopoietic diseases Hematology Humans Imatinib Imatinib Mesylate Inhibitor drugs Intensive Internal Medicine Intestinal Absorption Kinases Leukemia Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Medical sciences Medication Adherence Medicine Medicine & Public Health Myeloid leukemia Oncology Orosomucoid - metabolism Patients Pharmacodynamics Pharmacokinetics Pharmacology Piperazines - adverse effects Piperazines - pharmacokinetics Piperazines - therapeutic use Plasma Protein Binding Proteins Pyrimidines - adverse effects Pyrimidines - pharmacokinetics Pyrimidines - therapeutic use review Targeted cancer therapy Treatment Failure |
| title | Pharmacokinetic/pharmacodynamic correlation and blood-level testing in imatinib therapy for chronic myeloid leukemia |
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