Pharmacokinetics of PEGasparaginase in Infants with Acute Lymphoblastic Leukemia
Background PEGasparaginase is known to be a critical drug for treating pediatric acute lymphoblastic leukemia (ALL), however, there is insufficient evidence to determine the optimal dose for infants who are less than one year of age at diagnosis. This international study was conducted to identify th...
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| Veröffentlicht in: | Pharmaceutical research 2024-04, Vol.41 (4), p.711-720 |
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| creator | Brigitha, Leiah J. Mondelaers, Veerle Liu, Yiwei Albertsen, Birgitte K. Zalewska-Szewczyk, Beata Rizzari, Carmelo Kotecha, Rishi S. Pieters, Rob Huitema, Alwin D. R. van der Sluis, Inge M. |
| description | Background
PEGasparaginase is known to be a critical drug for treating pediatric acute lymphoblastic leukemia (ALL), however, there is insufficient evidence to determine the optimal dose for infants who are less than one year of age at diagnosis. This international study was conducted to identify the pharmacokinetics of PEGasparaginase in infants with newly diagnosed ALL and gather insight into the clearance and dosing of this population.
Methods
Infants with ALL who received treatment with PEGasparaginase were included in our population pharmacokinetic assessment employing non-linear mixed effects modelling (NONMEM).
Results
68 infants with ALL, with a total of 388 asparaginase activity samples, were included. PEGasparaginase doses ranging from 400 to 3,663 IU/m
2
were administered either intravenously or intramuscularly. A one-compartment model with time-dependent clearance, modeled using a transit model, provided the best fit to the data. Body weight was significantly correlated with clearance and volume of distribution. The final model estimated a half-life of 11.7 days just after administration, which decreased to 1.8 days 14 days after administration. Clearance was 19.5% lower during the post-induction treatment phase compared to induction.
Conclusion
The pharmacokinetics of PEGasparaginase in infants diagnosed under one year of age with ALL is comparable to that of older children (1–18 years). We recommend a PEGasparaginase dosing at 1,500 IU/m
2
for infants without dose adaptations according to age, and implementing therapeutic drug monitoring as standard practice. |
| doi_str_mv | 10.1007/s11095-024-03693-3 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_3014003666</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A790618078</galeid><sourcerecordid>A790618078</sourcerecordid><originalsourceid>FETCH-LOGICAL-c393t-272a978251a094e57f617b3b30d40afc96164282853feb5c82c533ac4bf71bab3</originalsourceid><addsrcrecordid>eNp9kUFr3DAQhUVpabZp_0APxdBLL05HlmRJxyWkSWChe0igNzHWSrtKbHkr2ZT8-yrZtKElBB0GNN8b3swj5COFEwogv2ZKQYsaGl4DazWr2SuyoEKyWgP_8ZosQJaWkpwekXc53wCAopq_JUdMCaa0hAVZr3eYBrTjbYhuCjZXo6_WZ-eY95hwGyJmV4VYXUaPccrVrzDtqqWdJ1et7ob9bux6zEVXrdx864aA78kbj312Hx7rMbn-dnZ1elGvvp9fni5XtWWaTXUjG9RSNYIiaO6E9C2VHesYbDigt7qlLW9UU4x61wmrGisYQ8s7L2mHHTsmXw5z92n8Obs8mSFk6_oeoxvnbBhQDuUsbVvQz_-hN-OcYnFXKA7lYq0QT9QWe2dC9OOU0N4PNUupoaUKpCrUyTNUeZuyvB2j86H8_yNoDgKbxpyT82afwoDpzlAw9zGaQ4ymxGgeYjSsiD49Op67wW3-Sv7kVgB2AHJpxa1LTyu9MPY3TIClQQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3040157655</pqid></control><display><type>article</type><title>Pharmacokinetics of PEGasparaginase in Infants with Acute Lymphoblastic Leukemia</title><source>SpringerLink Journals - AutoHoldings</source><creator>Brigitha, Leiah J. ; Mondelaers, Veerle ; Liu, Yiwei ; Albertsen, Birgitte K. ; Zalewska-Szewczyk, Beata ; Rizzari, Carmelo ; Kotecha, Rishi S. ; Pieters, Rob ; Huitema, Alwin D. R. ; van der Sluis, Inge M.</creator><creatorcontrib>Brigitha, Leiah J. ; Mondelaers, Veerle ; Liu, Yiwei ; Albertsen, Birgitte K. ; Zalewska-Szewczyk, Beata ; Rizzari, Carmelo ; Kotecha, Rishi S. ; Pieters, Rob ; Huitema, Alwin D. R. ; van der Sluis, Inge M.</creatorcontrib><description>Background
PEGasparaginase is known to be a critical drug for treating pediatric acute lymphoblastic leukemia (ALL), however, there is insufficient evidence to determine the optimal dose for infants who are less than one year of age at diagnosis. This international study was conducted to identify the pharmacokinetics of PEGasparaginase in infants with newly diagnosed ALL and gather insight into the clearance and dosing of this population.
Methods
Infants with ALL who received treatment with PEGasparaginase were included in our population pharmacokinetic assessment employing non-linear mixed effects modelling (NONMEM).
Results
68 infants with ALL, with a total of 388 asparaginase activity samples, were included. PEGasparaginase doses ranging from 400 to 3,663 IU/m
2
were administered either intravenously or intramuscularly. A one-compartment model with time-dependent clearance, modeled using a transit model, provided the best fit to the data. Body weight was significantly correlated with clearance and volume of distribution. The final model estimated a half-life of 11.7 days just after administration, which decreased to 1.8 days 14 days after administration. Clearance was 19.5% lower during the post-induction treatment phase compared to induction.
Conclusion
The pharmacokinetics of PEGasparaginase in infants diagnosed under one year of age with ALL is comparable to that of older children (1–18 years). We recommend a PEGasparaginase dosing at 1,500 IU/m
2
for infants without dose adaptations according to age, and implementing therapeutic drug monitoring as standard practice.</description><identifier>ISSN: 0724-8741</identifier><identifier>EISSN: 1573-904X</identifier><identifier>DOI: 10.1007/s11095-024-03693-3</identifier><identifier>PMID: 38538970</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Acute lymphoblastic leukemia ; Acute lymphocytic leukemia ; Age ; Analysis ; Asparaginase ; Biochemistry ; Biomedical and Life Sciences ; Biomedical Engineering and Bioengineering ; Biomedicine ; Body weight ; Cancer ; Care and treatment ; Dosage ; Drug dosages ; Infants ; Leukemia ; Lymphatic leukemia ; Medical Law ; Original Research Article ; Pediatrics ; Pharmacokinetics ; Pharmacology/Toxicology ; Pharmacy</subject><ispartof>Pharmaceutical research, 2024-04, Vol.41 (4), p.711-720</ispartof><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.</rights><rights>COPYRIGHT 2024 Springer</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c393t-272a978251a094e57f617b3b30d40afc96164282853feb5c82c533ac4bf71bab3</cites><orcidid>0000-0003-2816-2610</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11095-024-03693-3$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11095-024-03693-3$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38538970$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Brigitha, Leiah J.</creatorcontrib><creatorcontrib>Mondelaers, Veerle</creatorcontrib><creatorcontrib>Liu, Yiwei</creatorcontrib><creatorcontrib>Albertsen, Birgitte K.</creatorcontrib><creatorcontrib>Zalewska-Szewczyk, Beata</creatorcontrib><creatorcontrib>Rizzari, Carmelo</creatorcontrib><creatorcontrib>Kotecha, Rishi S.</creatorcontrib><creatorcontrib>Pieters, Rob</creatorcontrib><creatorcontrib>Huitema, Alwin D. R.</creatorcontrib><creatorcontrib>van der Sluis, Inge M.</creatorcontrib><title>Pharmacokinetics of PEGasparaginase in Infants with Acute Lymphoblastic Leukemia</title><title>Pharmaceutical research</title><addtitle>Pharm Res</addtitle><addtitle>Pharm Res</addtitle><description>Background
PEGasparaginase is known to be a critical drug for treating pediatric acute lymphoblastic leukemia (ALL), however, there is insufficient evidence to determine the optimal dose for infants who are less than one year of age at diagnosis. This international study was conducted to identify the pharmacokinetics of PEGasparaginase in infants with newly diagnosed ALL and gather insight into the clearance and dosing of this population.
Methods
Infants with ALL who received treatment with PEGasparaginase were included in our population pharmacokinetic assessment employing non-linear mixed effects modelling (NONMEM).
Results
68 infants with ALL, with a total of 388 asparaginase activity samples, were included. PEGasparaginase doses ranging from 400 to 3,663 IU/m
2
were administered either intravenously or intramuscularly. A one-compartment model with time-dependent clearance, modeled using a transit model, provided the best fit to the data. Body weight was significantly correlated with clearance and volume of distribution. The final model estimated a half-life of 11.7 days just after administration, which decreased to 1.8 days 14 days after administration. Clearance was 19.5% lower during the post-induction treatment phase compared to induction.
Conclusion
The pharmacokinetics of PEGasparaginase in infants diagnosed under one year of age with ALL is comparable to that of older children (1–18 years). We recommend a PEGasparaginase dosing at 1,500 IU/m
2
for infants without dose adaptations according to age, and implementing therapeutic drug monitoring as standard practice.</description><subject>Acute lymphoblastic leukemia</subject><subject>Acute lymphocytic leukemia</subject><subject>Age</subject><subject>Analysis</subject><subject>Asparaginase</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedical Engineering and Bioengineering</subject><subject>Biomedicine</subject><subject>Body weight</subject><subject>Cancer</subject><subject>Care and treatment</subject><subject>Dosage</subject><subject>Drug dosages</subject><subject>Infants</subject><subject>Leukemia</subject><subject>Lymphatic leukemia</subject><subject>Medical Law</subject><subject>Original Research Article</subject><subject>Pediatrics</subject><subject>Pharmacokinetics</subject><subject>Pharmacology/Toxicology</subject><subject>Pharmacy</subject><issn>0724-8741</issn><issn>1573-904X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNp9kUFr3DAQhUVpabZp_0APxdBLL05HlmRJxyWkSWChe0igNzHWSrtKbHkr2ZT8-yrZtKElBB0GNN8b3swj5COFEwogv2ZKQYsaGl4DazWr2SuyoEKyWgP_8ZosQJaWkpwekXc53wCAopq_JUdMCaa0hAVZr3eYBrTjbYhuCjZXo6_WZ-eY95hwGyJmV4VYXUaPccrVrzDtqqWdJ1et7ob9bux6zEVXrdx864aA78kbj312Hx7rMbn-dnZ1elGvvp9fni5XtWWaTXUjG9RSNYIiaO6E9C2VHesYbDigt7qlLW9UU4x61wmrGisYQ8s7L2mHHTsmXw5z92n8Obs8mSFk6_oeoxvnbBhQDuUsbVvQz_-hN-OcYnFXKA7lYq0QT9QWe2dC9OOU0N4PNUupoaUKpCrUyTNUeZuyvB2j86H8_yNoDgKbxpyT82afwoDpzlAw9zGaQ4ymxGgeYjSsiD49Op67wW3-Sv7kVgB2AHJpxa1LTyu9MPY3TIClQQ</recordid><startdate>20240401</startdate><enddate>20240401</enddate><creator>Brigitha, Leiah J.</creator><creator>Mondelaers, Veerle</creator><creator>Liu, Yiwei</creator><creator>Albertsen, Birgitte K.</creator><creator>Zalewska-Szewczyk, Beata</creator><creator>Rizzari, Carmelo</creator><creator>Kotecha, Rishi S.</creator><creator>Pieters, Rob</creator><creator>Huitema, Alwin D. R.</creator><creator>van der Sluis, Inge M.</creator><general>Springer US</general><general>Springer</general><general>Springer Nature B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-2816-2610</orcidid></search><sort><creationdate>20240401</creationdate><title>Pharmacokinetics of PEGasparaginase in Infants with Acute Lymphoblastic Leukemia</title><author>Brigitha, Leiah J. ; Mondelaers, Veerle ; Liu, Yiwei ; Albertsen, Birgitte K. ; Zalewska-Szewczyk, Beata ; Rizzari, Carmelo ; Kotecha, Rishi S. ; Pieters, Rob ; Huitema, Alwin D. R. ; van der Sluis, Inge M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c393t-272a978251a094e57f617b3b30d40afc96164282853feb5c82c533ac4bf71bab3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Acute lymphoblastic leukemia</topic><topic>Acute lymphocytic leukemia</topic><topic>Age</topic><topic>Analysis</topic><topic>Asparaginase</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedical Engineering and Bioengineering</topic><topic>Biomedicine</topic><topic>Body weight</topic><topic>Cancer</topic><topic>Care and treatment</topic><topic>Dosage</topic><topic>Drug dosages</topic><topic>Infants</topic><topic>Leukemia</topic><topic>Lymphatic leukemia</topic><topic>Medical Law</topic><topic>Original Research Article</topic><topic>Pediatrics</topic><topic>Pharmacokinetics</topic><topic>Pharmacology/Toxicology</topic><topic>Pharmacy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Brigitha, Leiah J.</creatorcontrib><creatorcontrib>Mondelaers, Veerle</creatorcontrib><creatorcontrib>Liu, Yiwei</creatorcontrib><creatorcontrib>Albertsen, Birgitte K.</creatorcontrib><creatorcontrib>Zalewska-Szewczyk, Beata</creatorcontrib><creatorcontrib>Rizzari, Carmelo</creatorcontrib><creatorcontrib>Kotecha, Rishi S.</creatorcontrib><creatorcontrib>Pieters, Rob</creatorcontrib><creatorcontrib>Huitema, Alwin D. R.</creatorcontrib><creatorcontrib>van der Sluis, Inge M.</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Pharmaceutical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Brigitha, Leiah J.</au><au>Mondelaers, Veerle</au><au>Liu, Yiwei</au><au>Albertsen, Birgitte K.</au><au>Zalewska-Szewczyk, Beata</au><au>Rizzari, Carmelo</au><au>Kotecha, Rishi S.</au><au>Pieters, Rob</au><au>Huitema, Alwin D. R.</au><au>van der Sluis, Inge M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pharmacokinetics of PEGasparaginase in Infants with Acute Lymphoblastic Leukemia</atitle><jtitle>Pharmaceutical research</jtitle><stitle>Pharm Res</stitle><addtitle>Pharm Res</addtitle><date>2024-04-01</date><risdate>2024</risdate><volume>41</volume><issue>4</issue><spage>711</spage><epage>720</epage><pages>711-720</pages><issn>0724-8741</issn><eissn>1573-904X</eissn><abstract>Background
PEGasparaginase is known to be a critical drug for treating pediatric acute lymphoblastic leukemia (ALL), however, there is insufficient evidence to determine the optimal dose for infants who are less than one year of age at diagnosis. This international study was conducted to identify the pharmacokinetics of PEGasparaginase in infants with newly diagnosed ALL and gather insight into the clearance and dosing of this population.
Methods
Infants with ALL who received treatment with PEGasparaginase were included in our population pharmacokinetic assessment employing non-linear mixed effects modelling (NONMEM).
Results
68 infants with ALL, with a total of 388 asparaginase activity samples, were included. PEGasparaginase doses ranging from 400 to 3,663 IU/m
2
were administered either intravenously or intramuscularly. A one-compartment model with time-dependent clearance, modeled using a transit model, provided the best fit to the data. Body weight was significantly correlated with clearance and volume of distribution. The final model estimated a half-life of 11.7 days just after administration, which decreased to 1.8 days 14 days after administration. Clearance was 19.5% lower during the post-induction treatment phase compared to induction.
Conclusion
The pharmacokinetics of PEGasparaginase in infants diagnosed under one year of age with ALL is comparable to that of older children (1–18 years). We recommend a PEGasparaginase dosing at 1,500 IU/m
2
for infants without dose adaptations according to age, and implementing therapeutic drug monitoring as standard practice.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>38538970</pmid><doi>10.1007/s11095-024-03693-3</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0003-2816-2610</orcidid></addata></record> |
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| ispartof | Pharmaceutical research, 2024-04, Vol.41 (4), p.711-720 |
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| source | SpringerLink Journals - AutoHoldings |
| subjects | Acute lymphoblastic leukemia Acute lymphocytic leukemia Age Analysis Asparaginase Biochemistry Biomedical and Life Sciences Biomedical Engineering and Bioengineering Biomedicine Body weight Cancer Care and treatment Dosage Drug dosages Infants Leukemia Lymphatic leukemia Medical Law Original Research Article Pediatrics Pharmacokinetics Pharmacology/Toxicology Pharmacy |
| title | Pharmacokinetics of PEGasparaginase in Infants with Acute Lymphoblastic Leukemia |
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