ArticleClinical pharmacokinetics2014
Characterisation of the clinical pharmacokinetics of actinomycin D and the influence of ABCB1 pharmacogenetic variation on actinomycin D disposition in children with cancer.
Article in Clinical pharmacokinetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- Clinical pharmacology of cytotoxic drugs in neonates and infants: Providing evidence-based dosing guidance.European journal of cancer (Oxford, England : 1990) · 2022Pooled it
- Cyclophosphamide pharmacokinetics and pharmacogenetics in children with B-cell non-Hodgkin's lymphoma.European journal of cancer (Oxford, England : 1990) · 2016Trial
- Dosing chemotherapy in children with obesity: literature review and evaluation of local practices.Cancer chemotherapy and pharmacology · 2025Review
- Suppressing proteasome activity enhances sensitivity to actinomycin D in diffuse anaplastic Wilms tumor.Cell reports. Medicine · 2025Article
- Actinomycin D and bortezomib disrupt protein homeostasis in Wilms tumor.bioRxiv : the preprint server for biology · 2024Article
- A Multidisciplinary Hyper-Modeling Scheme in Personalized In Silico Oncology: Coupling Cell Kinetics with Metabolism, Signaling Networks, and Biomechanics as Plug-In Component Models of a Cancer Digital Twin.Journal of personalized medicine · 2024Article
- Rhabdomyosarcoma: Current Therapy, Challenges, and Future Approaches to Treatment Strategies.Cancers · 2023Review
- Article
- Role of Drug Transporters in Elucidating Inter-Individual Variability in Pediatric Chemotherapy-Related Toxicities and Response.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Indispensable role of microbes in anticancer drugs and discovery trends.Applied microbiology and biotechnology · 2022Review
- The Impact of Pharmacogenetics on Pharmacokinetics and Pharmacodynamics in Neonates and Infants: A Systematic Review.Pharmacogenomics and personalized medicine · 2022Review
- Article
- Toxicity and pharmacokinetics of actinomycin-D and vincristine in children and adolescents: Children's Oncology Group Study ADVL06B1.Cancer chemotherapy and pharmacology · 2021Article
- Pharmacokinetics and Pharmacogenetics of Cyclophosphamide in a Neonate and Infant Childhood Cancer Patient Population.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Involvement of Reactive Oxygen Species in the Hepatorenal Toxicity of Actinomycin V In Vitro and In Vivo.Marine drugs · 2020Article
- Parthenolide as Cooperating Agent for Anti-Cancer Treatment of Various Malignancies.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Intestinal stenosis in Crohn's disease shows a generalized upregulation of genes involved in collagen metabolism and recognition that could serve as novel anti-fibrotic drug targets.Therapeutic advances in gastroenterology · 2020Article
- Identification of anti-flaviviral drugs with mosquitocidal and anti-Zika virus activity in Aedes aegypti.PLoS neglected tropical diseases · 2019Article
- Quantitative Chemotherapeutic Profiling of Gynecologic Cancer Cell Lines Using Approved Drugs and Bioactive Compounds.Translational oncology · 2019Article
- Actinomycin D-Activated RNase L Promotes H2A.X/H2B-Mediated DNA Damage and Apoptosis in Lung Cancer Cells.Frontiers in oncology · 2019Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
BACKGROUND AND
objectiveDespite its important role in cancer treatment, there is currently very limited available information concerning the clinical pharmacology of actinomycin D (Act D). The study was designed to characterise Act D pharmacokinetics and investigate the impact of pharmacogenetic variation on Act D disposition in children with cancer.
methodsA total of 650 plasma samples collected over an 8 year period from 117 patients ≤21 years receiving Act D (0.4-1.6 mg/m(2)) were used to characterise a population pharmacokinetic model. Polymorphisms in ABCB1 were analysed in 140 patients.
resultsA 3-compartment model provided a good fit to the data. Median values for Act D clearance and volume of distribution in the central compartment (V 1) obtained from the model were 5.3 L/h and 1.9 L (13.9 L/h/70 kg and 7.5 L/70 kg), respectively. There was substantial inter-subject variation in all pharmacokinetic parameters (coefficients of variation 53-81 % for non-normalised values). Body weight was a major determinant of Act D clearance, such that dose capping at 2 mg in larger children at a protocol dose of 1.5 mg/m(2) resulted in significantly lower area under the plasma concentration-time curves (mean AUC values: 9.3 versus 12.8 mg·min/L; P < 0.0001). No significant relationships were found between ABCB1 genetic variants and Act D pharmacokinetic parameters, nor between CL, V 1 or dose and incidence of grade 3 or 4 toxicity.
conclusionWe have defined the pharmacokinetics of Act D in a paediatric patient population, providing robust estimates of key pharmacokinetic parameters. Pharmacokinetic data bring into question the current clinical practice of dose capping at 2 mg in larger patients. Pharmacogenetic variation in candidate drug transporter genes identified from preclinical studies does not significantly impact on Act D exposure in a clinical setting.
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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.