ArticleCPT: pharmacometrics & systems pharmacology2013
Development of a Physiologically-Based Pharmacokinetic Model for Sirolimus: Predicting Bioavailability Based on Intestinal CYP3A Content.
Article in CPT: pharmacometrics & systems pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it.
- 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
- Characterizing the Developmental Trajectory of Sirolimus Clearance in Neonates and Infants.CPT: pharmacometrics & systems pharmacology · 2016Trial
- Optimal dosing for vascular anomalies paediatric patients with population pharmacokinetic model of sirolimus.British journal of clinical pharmacology · 2026Article
- Review
- Machine Learning Models Reveal New Risk Factors for Sub-/Supra-Therapeutic Concentrations of Sirolimus in Children with Vascular Anomalies.Drug design, development and therapy · 2026Article
- From Elixirs to Geroscience: A Historical and Molecular Perspective on Anti-Aging Medicine.Molecules (Basel, Switzerland) · 2025Review
- Sirolimus for the treatment of Graves' orbitopathy.Thyroid research · 2025Review
- The bioavailability and blood levels of low-dose rapamycin for longevity in real-world cohorts of normative aging individuals.GeroScience · 2025Article
- Long-term neuropsychologic outcome of pre-emptive mTOR inhibitor treatment in children with tuberous sclerosis complex (TSC) under 4 months of age (PROTECT), a two-arm, randomized, observer-blind, controlled phase IIb national multicentre clinical trial: study protocol.Orphanet journal of rare diseases · 2025Article
- Population pharmacokinetic study in children with vascular anomalies: body weight as a key variable in predicting the initial dose and dosing frequency of sirolimus.Frontiers in pharmacology · 2024Article
- Application of physiologically based pharmacokinetics modeling in the research of small-molecule targeted anti-cancer drugs.Cancer chemotherapy and pharmacology · 2023Review
- Pharmacokinetic and Pharmacodynamic Drug-Drug Interactions: Research Methods and Applications.Metabolites · 2023Review
- Multidrug-Loaded Lipid Nanoemulsions for the Combinatorial Treatment of Cerebral Cavernous Malformation Disease.Biomedicines · 2023Article
- Precision sirolimus dosing in children: The potential for model-informed dosing and novel drug monitoring.Frontiers in pharmacology · 2023Review
- Monitoring of sirolimus in the whole blood samples from pediatric patients with lymphatic anomalies.Open medicine (Warsaw, Poland) · 2023Article
- Rapamycin nanoparticles improves drug bioavailability in PLAM treatment by interstitial injection.Orphanet journal of rare diseases · 2022Article
- The Multifaceted Roles of Autophagy in Infectious, Obstructive, and Malignant Airway Diseases.Biomedicines · 2022Review
- Safety Profile of Rapamycin Perfluorocarbon Nanoparticles for Preventing Cisplatin-Induced Kidney Injury.Nanomaterials (Basel, Switzerland) · 2022Article
- The Combination of Cell Cultured Technology and In Silico Model to Inform the Drug Development.Pharmaceutics · 2021Review
- Ultra-thin, high strength, antibiotic-eluting sutures for prevention of ophthalmic infection.Bioengineering & translational medicine · 2021Article
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sirolimus is an inhibitor of mammalian target of rapamycin (mTOR) and is increasingly being used in transplantation and cancer therapies. Sirolimus has low oral bioavailability and exhibits large pharmacokinetic variability. The underlying mechanisms for this variability have not been explored to a large extent. Sirolimus metabolism was characterized by in vitro intrinsic clearance estimation. Pathway contribution ranked from CYP3A4 > CYP3A5 > CYP2C8. With the well stirred and Qgut models sirolimus bioavailability was predicted at 15%. Interindividual differences in bioavailability could be attributed to variable intestinal CYP3A expression. The physiologically-based pharmacokinetics (PBPK) model developed in Simcyp predicted a high distribution of sirolimus into adipose tissue and another elimination pathway in addition to CYP-mediated metabolism. PBPK model predictive performance was acceptable with Cmax and area under the curve (AUC) estimates within 20% of observed data in a dose escalation study. The model also showed potential to assess the impact of hepatic impairment and drug-drug interaction (DDI) on sirolimus pharmacokinetics.CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e59; doi:10.1038/psp.2013.33; published online 24 July 2013.
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Registered trials
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