ArticlePharmaceutical research2010
Influence of dosing schedule on organ exposure to cyclosporin in pediatric hematopoietic stem cell transplantation: analysis with a PBPK model.
Article in Pharmaceutical research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
7 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- Physiologically Based Pharmacokinetic (PBPK) Modeling and Simulation Approaches: A Systematic Review of Published Models, Applications, and Model Verification.Drug metabolism and disposition: the biological fate of chemicals · 2015Pooled it
- Physiologically-Based Pharmacokinetic Modeling to Support Pediatric Clinical Development: An IQ Working Group Perspective on the Current Status and Challenges.CPT: pharmacometrics & systems pharmacology · 2026Review
- Comparing Predictions of a PBPK Model for Cyclosporine With Drug Levels From Therapeutic Drug Monitoring.Frontiers in pharmacology · 2021Article
- Article
- Pharmacokinetics, Pharmacodynamics and Pharmacogenomics of Immunosuppressants in Allogeneic Haematopoietic Cell Transplantation: Part I.Clinical pharmacokinetics · 2016Review
- Confounding effect of cyclosporine dosing when comparing horse and rabbit antithymocyte globulin in patients with severe aplastic anemia.Haematologica · 2015Article
- Links between cyclosporin exposure in tissues and graft-versus-host disease in pediatric bone marrow transplantation: analysis by a PBPK model.Pharmaceutical research · 2011Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeCyclosporin is administered by intermittent infusions (II) or continuous infusions (CI) to prevent acute graft-versus-host disease (aGVHD). Because cyclosporin disposition is nonlinear, organ exposure may be higher after II than after CI, but saturation of receptors must be accounted for. The aim of the study was to compare both types of administration using a mechanistic model.
methodsA physiologically based pharmacokinetic model was developed to estimate cyclosporin exposure and receptor occupancies (RO) in aGVHD target organs and kidneys and to compare these estimations in pediatric patients that received cyclosporin either by II or CI. The relevant biological parameters were based on a clinical study in 2 groups of pediatric patients that received cyclosporin either by II (n = 31) or CI (n = 30).
resultsSimulations showed that the exposure to cyclosporin in the interstitial fluid of aGVHD target organs was greater at day 1 after II than after CI. In kidneys, the opposite order was observed. AUC(RO) in all organs was greater after CI than after II. The therapeutic index (the ratio of AUC(RO) in blood to AUC(RO) in kidneys) was greater with CI than with II.
conclusionsCI may be slightly more favorable than II for aGVHD prevention.
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Registered trials
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