ArticleBMJ open2013
Mathematical modelling to restore circulating IGF-1 concentrations in children with Crohn's disease-induced growth failure: a pharmacokinetic study.
Article in BMJ open, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 16 citations in OpenAlex.
- CMINNs: Compartment model informed neural networks - Unlocking drug dynamics.Computers in biology and medicine · 2025Article
- Growth Delay in Inflammatory Bowel Diseases: Significance, Causes, and Management.Digestive diseases and sciences · 2021Review
- Pharmacokinetic-Pharmacodynamic Modeling in Pediatric Drug Development, and the Importance of Standardized Scaling of Clearance.Clinical pharmacokinetics · 2019Review
- Up-regulation of IGF Binding Protein-3 Inhibits Colonic Inflammatory Response.Journal of Korean medical science · 2018Article
- Promising Biomarkers of Environmental Enteric Dysfunction: A Prospective Cohort study in Pakistani Children.Scientific reports · 2018Article
- Understanding and applying pharmacometric modelling and simulation in clinical practice and research.British journal of clinical pharmacology · 2017Review
- Assessing the feasibility of injectable growth-promoting therapy in Crohn's disease.Pilot and feasibility studies · 2016Article
- Endocrine therapy for growth retardation in paediatric inflammatory bowel disease.Paediatric drugs · 2014Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
objectivesChildren with Crohn's disease grow poorly, and inflammation depresses the response of insulin-like growth factor-1 (IGF-1) to growth hormone. Correcting the inflammation normalises growth velocity; however, removing inflammation cannot be achieved in all children. Our lack of understanding of IGF-1 kinetics has hampered its use, particularly as high IGF-1 concentrations over long periods may predispose to colon cancer. We hypothesised that mathematical modelling of IGF-1 would define dosing regimes that return IGF-1 concentrations into the normal range, without reaching values that risk cancer.
designPharmacokinetic intervention study.
settingTertiary paediatric gastroenterology unit.
participants8 children (M:F; 4:4) entered the study. All completed: 5 South Asian British; 2 White British; 1 African British. INCLUSION CRITERIA: Children over 10 years with active Crohn's disease (C reactive protein >10 mg/l or erythrocyte sedimentation rate >25 mm/h) and height velocity <-2 SD score. EXCLUSION CRITERIA: closed epiphyses; corticosteroids within 3 months; neoplasia or known hypersensitivity to recombinant human IGF-1 (rhIGF-1).
interventionsSubcutaneous rhIGF-1 (120 μg/kg) per dose over two admissions: the first as a single dose and the second as twice daily doses over 5 days. PRIMARY OUTCOME: Significant increase in circulating IGF-1. SECONDARY OUTCOMES: Incidence of side effects of IGF-1. A mathematical model of circulating IGF-1 (Ac) was developed to include parameters of endogenous synthesis (Ksyn); exogenous uptake (Ka) from the subcutaneous dose (As): and IGF-1 clearance: where dAc/dt=Ksyn - Kout×Ac+Ka×As.
resultsSubcutaneous IGF-1 increased concentrations, which were maintained on twice daily doses. In covariate analysis, disease activity reduced Ksyn (p<0.001). Optimal dosing was derived from least squares regression fitted to a dataset of 384 Crohn's patients, with model parameters assigned by simulation.
conclusionsBy using age, weight and disease activity scaling in IGF-1 dosing, over 95% of children will have normalised IGF-1 concentrations below +2.5 SDs of the normal population mean, a level not associated with cancer risk.
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