ArticleHaematologica2021
Individualized dosing guidelines for PEGasparaginase and factors influencing the clearance: a population pharmacokinetic model.
Article in Haematologica, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 16 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Pooled it
- Clinical pharmacology of cytotoxic drugs in neonates and infants: Providing evidence-based dosing guidance.European journal of cancer (Oxford, England : 1990) · 2022Pooled it
- Activity and toxicity of intramuscular 1000 iu/mBritish journal of haematology · 2022Trial
- Impact of Antibodies Against Polyethylene Glycol on the Pharmacokinetics of PEGylated Asparaginase in Children with Acute Lymphoblastic Leukaemia: A Population Pharmacokinetic Approach.European journal of drug metabolism and pharmacokinetics · 2022Trial
- Population Pharmacokinetics of PEGylated Asparaginase in Children with Acute Lymphoblastic Leukemia: Treatment Phase Dependency and Predictivity in Case of Missing Data.European journal of drug metabolism and pharmacokinetics · 2021Trial
- Toward adaptive therapeutic timing: integration of mechanistic pharmacology and artificial intelligence in precision dosing.Frontiers in pharmacology · 2026Review
- Early prediction of subsequent peg-asparaginase inactivation in acute lymphoblastic leukaemia patients-A NOPHO ALL2008 study.British journal of haematology · 2025Observational
- PEGylated Asparaginase in Children with Acute Lymphoblastic Leukemia Treated within the AIEOP-BFM ALL 2009 Trial: Population Pharmacokinetics and Drug Exposure.European journal of drug metabolism and pharmacokinetics · 2025Article
- Pharmacokinetics of Pegaspargase with a Limited Sampling Strategy for Asparaginase Activity Monitoring in Children with Acute Lymphoblastic Leukemia.Pharmaceutics · 2025Article
- Review
- Adverse Impacts of PEGylated Protein Therapeutics: A Targeted Literature Review.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024Review
- Increase in peg-asparaginase clearance as a predictor for inactivation in patients with acute lymphoblastic leukemia.Leukemia · 2024Article
- Determination of l-Asparaginase Activity and Its Therapeutic Monitoring in Children with Hematological Malignancies in a Single Croatian Center.Diagnostics (Basel, Switzerland) · 2024Article
- Individualized dosing guidelines for PEGasparaginase and factors influencing the clearance: a population pharmacokinetic model.Haematologica · 2023Article
- Asparaginase in the Treatment of Acute Lymphoblastic Leukemia in Adults: Current Evidence and Place in Therapy.Blood and lymphatic cancer : targets and therapy · 2022Review
- Article
Corrections and comments
- Erratum issued
Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Considerable inter- and intra-patient variability exist in serum activity levels of PEGasparaginase, essential for pediatric acute lymphoblastic leukemia treatment. A population pharmacokinetic (popPK) model was developed, identifying patient characteristics explaining these variabilities. Patients (n=92) were treated according to the DCOG ALL-11 protocol, using therapeutic drug monitoring to individualize the PEGasparaginase doses. Non-linear mixed effects modeling (NONMEM) was used to analyze the popPK evaluating several covariates. The final model was validated using an independent database (n=28). Guidelines for starting doses and dose adjustments were developed. A one-compartment model with time-dependent clearance adequately described the popPK. Normalization of clearance and volume of distribution by body surface are (BSA) reduced inter-individual variability. Clearance was 0.084 L/day/m2 for 12.7 days, increasing with 0.082 L/day/m2/day thereafter. Clearance was 38% higher during an infection, and 11-19% higher during induction treatment than intensification and maintenance (p<0.001). Targeting an asparaginase activity level of 100 IU/L, a loading dose of 800 IU/m2 (induction) and 600 IU/m2 (intensification) is advised. In conclusion, variability of PEGasparaginase activity levels can be explained by BSA, treatment phase and the occurrence of an infection. With this popPK model, PEGasparaginase treatment can be individualized further, taking into account these covariates and the dosing guidelines provided.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.