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Pharmacokinetics of daunorubicin and daunorubicinol in infants with leukemia treated in the interfant 99 protocol
Background There is an extreme paucity of pharmacokinetic data for anticancer agents in infants. Therefore, we aimed at characterizing the pharmacokinetics for daunorubicin in infants and examined their relationship to age, body weight, and body surface area. Procedure Leukemia patients treated acco...
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| Published in: | Pediatric blood & cancer 2010-03, Vol.54 (3), p.355-360 |
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| container_end_page | 360 |
| container_issue | 3 |
| container_start_page | 355 |
| container_title | Pediatric blood & cancer |
| container_volume | 54 |
| creator | Hempel, Georg Relling, Mary V. de Rossi, Giulio Stary, Jan De Lorenzo, Paola Valsecchi, Maria Grazia Barisone, Elena Boos, Joachim Pieters, Rob |
| description | Background
There is an extreme paucity of pharmacokinetic data for anticancer agents in infants. Therefore, we aimed at characterizing the pharmacokinetics for daunorubicin in infants and examined their relationship to age, body weight, and body surface area.
Procedure
Leukemia patients treated according to the Interfant 99 protocol received 30 mg/m2 daunorubicin, with dose reduction to 3/4 for patients 6–12 months old and 2/3 for patients |
| doi_str_mv | 10.1002/pbc.22266 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1020842618</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1020842618</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3956-5d8426d49da571a4de5e8f8aff73e9276d5aacd7ab713c13596cfb93ac51e1b13</originalsourceid><addsrcrecordid>eNp10E1v1DAQBmALUdEPOPAHkI9wSGvHayc-0lVpQVVbIRBHa2JPtGaTeGs7Kv33eNmlFQdOY1nPvCO9hLzl7JQzVp9tOnta17VSL8gRlwtZScabl09vpg_JcUo_C1VMtq_IIdeN4ILrI3J_t4I4gg1rP2H2NtHQUwfzFOLceesnCpP75yMMtPz6qYcpJ_rg84oOOK9x9EBzRMjotiCvsIyMceuo1nQTQw42DK_JQQ9Dwjf7eUK-f7r4tryqrm8vPy8_XldWaKkq6dpFrdxCO5ANh4VDiW3fQt83AnXdKCcBrGuga7iwXEitbN9pAVZy5B0XJ-T9Lrccvp8xZTP6ZHEYYMIwJ8NZzbYneFvohx21MaQUsTeb6EeIjwWZbcOmNGz-NFzsu33s3I3onuW-0gLOduDBD_j4_yRzd778G1ntNnzK-OtpA-LaqEY00vy4uTT1l_OvXDJltPgN-HmWAQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1020842618</pqid></control><display><type>article</type><title>Pharmacokinetics of daunorubicin and daunorubicinol in infants with leukemia treated in the interfant 99 protocol</title><source>Wiley-Blackwell Read & Publish Collection</source><creator>Hempel, Georg ; Relling, Mary V. ; de Rossi, Giulio ; Stary, Jan ; De Lorenzo, Paola ; Valsecchi, Maria Grazia ; Barisone, Elena ; Boos, Joachim ; Pieters, Rob</creator><creatorcontrib>Hempel, Georg ; Relling, Mary V. ; de Rossi, Giulio ; Stary, Jan ; De Lorenzo, Paola ; Valsecchi, Maria Grazia ; Barisone, Elena ; Boos, Joachim ; Pieters, Rob</creatorcontrib><description>Background
There is an extreme paucity of pharmacokinetic data for anticancer agents in infants. Therefore, we aimed at characterizing the pharmacokinetics for daunorubicin in infants and examined their relationship to age, body weight, and body surface area.
Procedure
Leukemia patients treated according to the Interfant 99 protocol received 30 mg/m2 daunorubicin, with dose reduction to 3/4 for patients 6–12 months old and 2/3 for patients <6 months, respectively. Plasma samples from 21 patients (aged 0.05–1.88 years) were collected and analyzed for daunorubicin and daunorubicinol. Samples from 12 children (age 1.6–18.8 years), who received daunorubicin in an earlier investigation, were used for pharmacokinetic model building using the software NONMEM.
Results
Plasma concentration time profiles could be described using a two compartment model. Daunorubicin clearance was 43.9 L hr−1 m−2 ± 65% and central volume of distribution 16.4 L m−2 ± 46%, whereas apparent clearance of daunorubicinol was 19.1 L hr−1 m−2 ± 32% and apparent volume of distribution 228 L m−2 ± 80% (mean ± interindividual variability). No age‐dependency in any of the BSA‐normalized pharmacokinetic parameters was observed. Consequently, due to the empirical dose reduction in infants the overall exposure to daunorubicinol in infants was smaller than would be expected from older children. Patients aged <6 months experienced more infections in the induction phase than the group aged 6–12 months at diagnosis. Other toxicities were similar in both groups.
Conclusion
We observed no indication of an age‐dependency in the pharmacokinetics of daunorubicin. Pediatr Blood Cancer 2010;54:355–360. © 2009 Wiley‐Liss, Inc.</description><identifier>ISSN: 1545-5009</identifier><identifier>ISSN: 1545-5017</identifier><identifier>EISSN: 1545-5017</identifier><identifier>DOI: 10.1002/pbc.22266</identifier><identifier>PMID: 19731319</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Adolescent ; Age ; Age Factors ; Antibiotics, Antineoplastic - administration & dosage ; Antibiotics, Antineoplastic - adverse effects ; Antibiotics, Antineoplastic - blood ; Antibiotics, Antineoplastic - pharmacokinetics ; Antitumor agents ; Blood ; Body weight ; Cancer ; Child ; Child, Preschool ; Children ; Computer programs ; Data processing ; Daunorubicin ; Daunorubicin - administration & dosage ; Daunorubicin - adverse effects ; Daunorubicin - analogs & derivatives ; Daunorubicin - blood ; Daunorubicin - pharmacokinetics ; Female ; Humans ; Infant ; Infant, Newborn ; Infants ; Infection ; Leukemia ; Male ; Pharmacokinetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - blood ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy ; software ; Surface area ; Toxicity</subject><ispartof>Pediatric blood & cancer, 2010-03, Vol.54 (3), p.355-360</ispartof><rights>Copyright © 2009 Wiley‐Liss, Inc.</rights><rights>Copyright 2009 Wiley-Liss, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3956-5d8426d49da571a4de5e8f8aff73e9276d5aacd7ab713c13596cfb93ac51e1b13</citedby><cites>FETCH-LOGICAL-c3956-5d8426d49da571a4de5e8f8aff73e9276d5aacd7ab713c13596cfb93ac51e1b13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19731319$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hempel, Georg</creatorcontrib><creatorcontrib>Relling, Mary V.</creatorcontrib><creatorcontrib>de Rossi, Giulio</creatorcontrib><creatorcontrib>Stary, Jan</creatorcontrib><creatorcontrib>De Lorenzo, Paola</creatorcontrib><creatorcontrib>Valsecchi, Maria Grazia</creatorcontrib><creatorcontrib>Barisone, Elena</creatorcontrib><creatorcontrib>Boos, Joachim</creatorcontrib><creatorcontrib>Pieters, Rob</creatorcontrib><title>Pharmacokinetics of daunorubicin and daunorubicinol in infants with leukemia treated in the interfant 99 protocol</title><title>Pediatric blood & cancer</title><addtitle>Pediatr. Blood Cancer</addtitle><description>Background
There is an extreme paucity of pharmacokinetic data for anticancer agents in infants. Therefore, we aimed at characterizing the pharmacokinetics for daunorubicin in infants and examined their relationship to age, body weight, and body surface area.
Procedure
Leukemia patients treated according to the Interfant 99 protocol received 30 mg/m2 daunorubicin, with dose reduction to 3/4 for patients 6–12 months old and 2/3 for patients <6 months, respectively. Plasma samples from 21 patients (aged 0.05–1.88 years) were collected and analyzed for daunorubicin and daunorubicinol. Samples from 12 children (age 1.6–18.8 years), who received daunorubicin in an earlier investigation, were used for pharmacokinetic model building using the software NONMEM.
Results
Plasma concentration time profiles could be described using a two compartment model. Daunorubicin clearance was 43.9 L hr−1 m−2 ± 65% and central volume of distribution 16.4 L m−2 ± 46%, whereas apparent clearance of daunorubicinol was 19.1 L hr−1 m−2 ± 32% and apparent volume of distribution 228 L m−2 ± 80% (mean ± interindividual variability). No age‐dependency in any of the BSA‐normalized pharmacokinetic parameters was observed. Consequently, due to the empirical dose reduction in infants the overall exposure to daunorubicinol in infants was smaller than would be expected from older children. Patients aged <6 months experienced more infections in the induction phase than the group aged 6–12 months at diagnosis. Other toxicities were similar in both groups.
Conclusion
We observed no indication of an age‐dependency in the pharmacokinetics of daunorubicin. Pediatr Blood Cancer 2010;54:355–360. © 2009 Wiley‐Liss, Inc.</description><subject>Adolescent</subject><subject>Age</subject><subject>Age Factors</subject><subject>Antibiotics, Antineoplastic - administration & dosage</subject><subject>Antibiotics, Antineoplastic - adverse effects</subject><subject>Antibiotics, Antineoplastic - blood</subject><subject>Antibiotics, Antineoplastic - pharmacokinetics</subject><subject>Antitumor agents</subject><subject>Blood</subject><subject>Body weight</subject><subject>Cancer</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Children</subject><subject>Computer programs</subject><subject>Data processing</subject><subject>Daunorubicin</subject><subject>Daunorubicin - administration & dosage</subject><subject>Daunorubicin - adverse effects</subject><subject>Daunorubicin - analogs & derivatives</subject><subject>Daunorubicin - blood</subject><subject>Daunorubicin - pharmacokinetics</subject><subject>Female</subject><subject>Humans</subject><subject>Infant</subject><subject>Infant, Newborn</subject><subject>Infants</subject><subject>Infection</subject><subject>Leukemia</subject><subject>Male</subject><subject>Pharmacokinetics</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - blood</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy</subject><subject>software</subject><subject>Surface area</subject><subject>Toxicity</subject><issn>1545-5009</issn><issn>1545-5017</issn><issn>1545-5017</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><recordid>eNp10E1v1DAQBmALUdEPOPAHkI9wSGvHayc-0lVpQVVbIRBHa2JPtGaTeGs7Kv33eNmlFQdOY1nPvCO9hLzl7JQzVp9tOnta17VSL8gRlwtZScabl09vpg_JcUo_C1VMtq_IIdeN4ILrI3J_t4I4gg1rP2H2NtHQUwfzFOLceesnCpP75yMMtPz6qYcpJ_rg84oOOK9x9EBzRMjotiCvsIyMceuo1nQTQw42DK_JQQ9Dwjf7eUK-f7r4tryqrm8vPy8_XldWaKkq6dpFrdxCO5ANh4VDiW3fQt83AnXdKCcBrGuga7iwXEitbN9pAVZy5B0XJ-T9Lrccvp8xZTP6ZHEYYMIwJ8NZzbYneFvohx21MaQUsTeb6EeIjwWZbcOmNGz-NFzsu33s3I3onuW-0gLOduDBD_j4_yRzd778G1ntNnzK-OtpA-LaqEY00vy4uTT1l_OvXDJltPgN-HmWAQ</recordid><startdate>201003</startdate><enddate>201003</enddate><creator>Hempel, Georg</creator><creator>Relling, Mary V.</creator><creator>de Rossi, Giulio</creator><creator>Stary, Jan</creator><creator>De Lorenzo, Paola</creator><creator>Valsecchi, Maria Grazia</creator><creator>Barisone, Elena</creator><creator>Boos, Joachim</creator><creator>Pieters, Rob</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope></search><sort><creationdate>201003</creationdate><title>Pharmacokinetics of daunorubicin and daunorubicinol in infants with leukemia treated in the interfant 99 protocol</title><author>Hempel, Georg ; Relling, Mary V. ; de Rossi, Giulio ; Stary, Jan ; De Lorenzo, Paola ; Valsecchi, Maria Grazia ; Barisone, Elena ; Boos, Joachim ; Pieters, Rob</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3956-5d8426d49da571a4de5e8f8aff73e9276d5aacd7ab713c13596cfb93ac51e1b13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Adolescent</topic><topic>Age</topic><topic>Age Factors</topic><topic>Antibiotics, Antineoplastic - administration & dosage</topic><topic>Antibiotics, Antineoplastic - adverse effects</topic><topic>Antibiotics, Antineoplastic - blood</topic><topic>Antibiotics, Antineoplastic - pharmacokinetics</topic><topic>Antitumor agents</topic><topic>Blood</topic><topic>Body weight</topic><topic>Cancer</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Children</topic><topic>Computer programs</topic><topic>Data processing</topic><topic>Daunorubicin</topic><topic>Daunorubicin - administration & dosage</topic><topic>Daunorubicin - adverse effects</topic><topic>Daunorubicin - analogs & derivatives</topic><topic>Daunorubicin - blood</topic><topic>Daunorubicin - pharmacokinetics</topic><topic>Female</topic><topic>Humans</topic><topic>Infant</topic><topic>Infant, Newborn</topic><topic>Infants</topic><topic>Infection</topic><topic>Leukemia</topic><topic>Male</topic><topic>Pharmacokinetics</topic><topic>Precursor Cell Lymphoblastic Leukemia-Lymphoma - blood</topic><topic>Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy</topic><topic>software</topic><topic>Surface area</topic><topic>Toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hempel, Georg</creatorcontrib><creatorcontrib>Relling, Mary V.</creatorcontrib><creatorcontrib>de Rossi, Giulio</creatorcontrib><creatorcontrib>Stary, Jan</creatorcontrib><creatorcontrib>De Lorenzo, Paola</creatorcontrib><creatorcontrib>Valsecchi, Maria Grazia</creatorcontrib><creatorcontrib>Barisone, Elena</creatorcontrib><creatorcontrib>Boos, Joachim</creatorcontrib><creatorcontrib>Pieters, Rob</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Pediatric blood & cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hempel, Georg</au><au>Relling, Mary V.</au><au>de Rossi, Giulio</au><au>Stary, Jan</au><au>De Lorenzo, Paola</au><au>Valsecchi, Maria Grazia</au><au>Barisone, Elena</au><au>Boos, Joachim</au><au>Pieters, Rob</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pharmacokinetics of daunorubicin and daunorubicinol in infants with leukemia treated in the interfant 99 protocol</atitle><jtitle>Pediatric blood & cancer</jtitle><addtitle>Pediatr. Blood Cancer</addtitle><date>2010-03</date><risdate>2010</risdate><volume>54</volume><issue>3</issue><spage>355</spage><epage>360</epage><pages>355-360</pages><issn>1545-5009</issn><issn>1545-5017</issn><eissn>1545-5017</eissn><abstract>Background
There is an extreme paucity of pharmacokinetic data for anticancer agents in infants. Therefore, we aimed at characterizing the pharmacokinetics for daunorubicin in infants and examined their relationship to age, body weight, and body surface area.
Procedure
Leukemia patients treated according to the Interfant 99 protocol received 30 mg/m2 daunorubicin, with dose reduction to 3/4 for patients 6–12 months old and 2/3 for patients <6 months, respectively. Plasma samples from 21 patients (aged 0.05–1.88 years) were collected and analyzed for daunorubicin and daunorubicinol. Samples from 12 children (age 1.6–18.8 years), who received daunorubicin in an earlier investigation, were used for pharmacokinetic model building using the software NONMEM.
Results
Plasma concentration time profiles could be described using a two compartment model. Daunorubicin clearance was 43.9 L hr−1 m−2 ± 65% and central volume of distribution 16.4 L m−2 ± 46%, whereas apparent clearance of daunorubicinol was 19.1 L hr−1 m−2 ± 32% and apparent volume of distribution 228 L m−2 ± 80% (mean ± interindividual variability). No age‐dependency in any of the BSA‐normalized pharmacokinetic parameters was observed. Consequently, due to the empirical dose reduction in infants the overall exposure to daunorubicinol in infants was smaller than would be expected from older children. Patients aged <6 months experienced more infections in the induction phase than the group aged 6–12 months at diagnosis. Other toxicities were similar in both groups.
Conclusion
We observed no indication of an age‐dependency in the pharmacokinetics of daunorubicin. Pediatr Blood Cancer 2010;54:355–360. © 2009 Wiley‐Liss, Inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>19731319</pmid><doi>10.1002/pbc.22266</doi><tpages>6</tpages></addata></record> |
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| subjects | Adolescent Age Age Factors Antibiotics, Antineoplastic - administration & dosage Antibiotics, Antineoplastic - adverse effects Antibiotics, Antineoplastic - blood Antibiotics, Antineoplastic - pharmacokinetics Antitumor agents Blood Body weight Cancer Child Child, Preschool Children Computer programs Data processing Daunorubicin Daunorubicin - administration & dosage Daunorubicin - adverse effects Daunorubicin - analogs & derivatives Daunorubicin - blood Daunorubicin - pharmacokinetics Female Humans Infant Infant, Newborn Infants Infection Leukemia Male Pharmacokinetics Precursor Cell Lymphoblastic Leukemia-Lymphoma - blood Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy software Surface area Toxicity |
| title | Pharmacokinetics of daunorubicin and daunorubicinol in infants with leukemia treated in the interfant 99 protocol |
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