Population Pharmacokinetics of PEGylated Asparaginase in Children with Acute Lymphoblastic Leukemia: Treatment Phase Dependency and Predictivity in Case of Missing Data.
Adolescent
Antineoplastic Agents
/ administration & dosage
Area Under Curve
Asparaginase
/ administration & dosage
Child
Child, Preschool
Female
Humans
Infant
Male
Models, Biological
Polyethylene Glycols
/ administration & dosage
Precursor Cell Lymphoblastic Leukemia-Lymphoma
/ drug therapy
Tissue Distribution
Journal
European journal of drug metabolism and pharmacokinetics
ISSN: 2107-0180
Titre abrégé: Eur J Drug Metab Pharmacokinet
Pays: France
ID NLM: 7608491
Informations de publication
Date de publication:
Mar 2021
Mar 2021
Historique:
accepted:
22
01
2021
pubmed:
18
2
2021
medline:
3
11
2021
entrez:
17
2
2021
Statut:
ppublish
Résumé
The pharmacokinetics of polyethylene glycol-conjugated asparaginase (PEG-ASNase) are characterized by an increase in elimination over time, a marked increase in ASNase activity levels from induction to reinduction, and high inter- and intraindividual variability. A population pharmacokinetic (PopPK) model is required to estimate individual dose intensity, despite gaps in monitoring compliance. In the AIEOP-BFM ALL 2009 trial, two PEG-ASNase administrations (2500 U/m Compared to the first administration in induction (1374 patients, 6069 samples), the initial clearance and volume of distribution decreased by 11.0% and 15.9%, respectively, during the second administration during induction and by 41.2% and 28.4% during reinduction. Furthermore, the initial clearance linearly increased for children aged > 8 years and was 7.1% lower for females. The model was successfully externally validated (1253 patients, 5523 samples). In case of missing data, > 52% of the predictions for observations and > 82% for derived parameters were within ± 20% of the nominal value. A PopPK model that describes the complex pharmacokinetics of PEG-ASNase was successfully externally validated. AUC
Sections du résumé
BACKGROUND AND OBJECTIVES
OBJECTIVE
The pharmacokinetics of polyethylene glycol-conjugated asparaginase (PEG-ASNase) are characterized by an increase in elimination over time, a marked increase in ASNase activity levels from induction to reinduction, and high inter- and intraindividual variability. A population pharmacokinetic (PopPK) model is required to estimate individual dose intensity, despite gaps in monitoring compliance.
METHODS
METHODS
In the AIEOP-BFM ALL 2009 trial, two PEG-ASNase administrations (2500 U/m
RESULTS
RESULTS
Compared to the first administration in induction (1374 patients, 6069 samples), the initial clearance and volume of distribution decreased by 11.0% and 15.9%, respectively, during the second administration during induction and by 41.2% and 28.4% during reinduction. Furthermore, the initial clearance linearly increased for children aged > 8 years and was 7.1% lower for females. The model was successfully externally validated (1253 patients, 5523 samples). In case of missing data, > 52% of the predictions for observations and > 82% for derived parameters were within ± 20% of the nominal value.
CONCLUSION
CONCLUSIONS
A PopPK model that describes the complex pharmacokinetics of PEG-ASNase was successfully externally validated. AUC
Identifiants
pubmed: 33595793
doi: 10.1007/s13318-021-00670-8
pii: 10.1007/s13318-021-00670-8
pmc: PMC7935823
doi:
Substances chimiques
Antineoplastic Agents
0
Polyethylene Glycols
3WJQ0SDW1A
pegaspargase
7D96IR0PPM
Asparaginase
EC 3.5.1.1
Banques de données
ClinicalTrials.gov
['NCT01117441']
Types de publication
Clinical Trial
Journal Article
Multicenter Study
Validation Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
289-300Références
Asselin BL, Whitin JC, Coppola DJ, Rupp IP, Sallan SE, Cohen HJ. Comparative pharmacokinetic studies of three asparaginase preparations. J Clin Oncol. 1993;11(9):1780–6.
doi: 10.1200/JCO.1993.11.9.1780
Müller HJ, Löning L, Horn A, et al. Pegylated asparaginase (Oncaspar) in children with ALL: drug monitoring in reinduction according to the ALL/NHL-BFM 95 protocols. Br J Haematol. 2000;110(2):379–84.
doi: 10.1046/j.1365-2141.2000.02187.x
EU Clinical Trials Register. Dutch Childhood Oncology Group: Protocol ALL-11: Treatment study protocol of the Dutch Childhood Oncology Group for children and adolescents (1-19 year) with newly diagnosed acute lymphoblastic leukemia [online]. 2020. https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-000067-25/NL . Accessed 25 Sep 2020.
ClinicalTrials.gov. Dana-Farber Cancer Institute. Treatment of Newly Diagnosed Acute Lymphoblastic Leukemia in Children and Adolescents [online]. 2020. https://clinicaltrials.gov/ct2/show/record/NCT03020030?cond=ALL%2C+Childhood&view=record . Accessed 25 Sep 2020.
EU Clinical Trials Register. AIEOP-BFM ALL 2009: International collaborative treatment protocol for children and adolescents with acute lymphoblastic leukemia [online]. 2020. https://www.clinicaltrialsregister.eu/ctr-search/trial/2007-004270-43/DE . Accessed 25 Sep 2020.
Lanvers-Kaminsky C. Asparaginase pharmacology: challenges still to be faced. Cancer Chemother Pharmacol. 2017;79(3):439–50.
doi: 10.1007/s00280-016-3236-y
Food and Drug Administration. Oncaspar (pegaspargase) injection label. Revised 01/2019 [online]. 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/193411s5196lbl.pdf . Accessed 25 Sep 2020.
Kloos RQH, Pieters R, Jumelet FMV, de Groot-Kruseman HA, van den Bos C, van der Sluis IM. Individualized asparaginase dosing in childhood acute lymphoblastic leukemia. J Clin Oncol. 2020;38(7):715–24.
doi: 10.1200/JCO.19.02292
Kloos RQH, Mathôt R, Pieters R, van der Sluis IM. Individualized dosing guidelines for PEGasparaginase and factors influencing the clearance: a population pharmacokinetic model. Haematologica. 2020. https://doi.org/10.3324/haematol.2019.242289 .
doi: 10.3324/haematol.2019.242289
pubmed: 32327497
pmcid: 7049360
Würthwein G, Lanvers-Kaminsky C, Hempel G, et al. Population pharmacokinetics to model the time-varying clearance of the PEGylated Asparaginase Oncaspar® in children with acute lymphoblastic leukemia. Eur J Drug Metab Pharmacokinet. 2017;42(6):955–63.
doi: 10.1007/s13318-017-0410-5
Hempel G, Müller HJ, Lanvers-Kaminsky C, Würthwein G, Hoppe A, Boos J. A population pharmacokinetic model for pegylated-asparaginase in children. Br J Haematol. 2010;148(1):119–25.
doi: 10.1111/j.1365-2141.2009.07923.x
Würthwein G, Lanvers-Kaminsky C, Gerss J, et al. Therapeutic drug monitoring of asparaginase: intra-individual variability and predictivity in children with acute lymphoblastic leukemia treated with PEG-asparaginase in the AIEOP-BFM Acute Lymphoblastic Leukemia 2009 Study. Ther Drug Monit. 2020;42(3):435–44.
doi: 10.1097/FTD.0000000000000727
Lanvers C, Vieira Pinheiro JP, Hempel G, Wuerthwein G, Boos J. Analytical validation of a microplate reader-based method for the therapeutic drug monitoring of L-asparaginase in human serum. Anal Biochem. 2002;309(1):117–26.
doi: 10.1016/S0003-2697(02)00232-4
van der Sluis D, Vrooman LM, Pieters R, et al. Consensus expert recommendations for identification and management of asparaginase hypersensitivity and silent inactivation. Haematologica. 2016;101(3):279–85.
doi: 10.3324/haematol.2015.137380
R Core Team. R: A language and environment for statistical computing: a language and environment for statistical computing: R Foundation for Statistical Computing, Vienna, Austria; 2018.
Lindbom L, Pihlgren P, Jonsson EN. PsN-Toolkit—a collection of computer intensive statistical methods for non-linear mixed effect modeling using NONMEM. Comput Methods Programs Biomed. 2005;79(3):241–57.
doi: 10.1016/j.cmpb.2005.04.005
Keizer RJ, Karlsson MO, Hooker A. Modeling and Simulation Workbench for NONMEM: Tutorial on Pirana, PsN, and Xpose. CPT Pharmacometrics Syst Pharmacol. 2013;2:e50.
doi: 10.1038/psp.2013.24
Icon Development Solutions. NONMEM Users’s Guides: Ellicott City, Maryland; 2009.
Byon W, Smith MK, Chan P, et al. Establishing best practices and guidance in population modeling: an experience with an internal population pharmacokinetic analysis guidance. CPT Pharmacometrics Syst Pharmacol. 2013;2:e51.
doi: 10.1038/psp.2013.26
Mosteller RD. Simplified calculation of body-surface area. N Engl J Med. 1987;317(17):1098.
pubmed: 3657876
Broeker A, Nardecchia M, Klinker KP, et al. Towards precision dosing of vancomycin: a systematic evaluation of pharmacometric models for Bayesian forecasting. Clin Microbiol Infect. 2019;25(10):1286.e1-1286.e7.
doi: 10.1016/j.cmi.2019.02.029
Food and Drug Administration. Guidance for Industry. Draft Guidance 07/2019 [online]. 2020. https://www.fda.gov/media/128793/download . Accessed 4 Jan 2021.
Sun H, Fadiran EO, Jones CD, et al. Population pharmacokinetics. A regulatory perspective. Clin Pharmacokin. 1999;37(1):41–58.
doi: 10.2165/00003088-199937010-00003
Raes A, van Aken S, Craen M, Donckerwolcke R, Vande WJ. A reference frame for blood volume in children and adolescents. BMC Pediatr. 2006;6:3.
doi: 10.1186/1471-2431-6-3
European Medicines Agency. Guideline on bioanalytical method validation [online]. 2020. https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-bioanalytical-method-validation_en.pdf . Accessed 25 Sep 2020.