ArticlePharmaceutical research2021
Modeling Approach to Predict the Impact of Inflammation on the Pharmacokinetics of CYP2C19 and CYP3A4 Substrates.
Article in Pharmaceutical research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Associated factors with voriconazole plasma concentration: a systematic review and meta-analysis.Frontiers in pharmacology · 2024Pooled it
- Delayed decrease in voriconazole concentration after resolution of inflammation in a patient with invasive pulmonary aspergillosis: a case report.Journal of pharmaceutical health care and sciences · 2026Article
- The non-linear and linear effects of CYP2C19 metaboliser status on DNA methylation: a methylome-wide association study.Clinical epigenetics · 2026Article
- Changes in Antidepressant Absorption After Metabolic Bariatric Surgery.Obesity surgery · 2025Article
- Population pharmacokinetics and dose optimization of voriconazole in patients with COVID-19-associated pulmonary aspergillosis.Frontiers in pharmacology · 2025Article
- The relation between inflammatory biomarkers and drug pharmacokinetics in the critically ill patients: a scoping review.Critical care (London, England) · 2024Article
- Changes in Plasma Clearance of CYP450 Probe Drugs May Not be Specific for Altered In Vivo Enzyme Activity Under (Patho)Physiological Conditions: How to Interpret Findings of Probe Cocktail Studies.Clinical pharmacokinetics · 2024Article
- The combination of CYP2C19 polymorphism and inflammatory cell ratios in prognosis cardiac adverse events after acute coronary syndrome.International journal of cardiology. Cardiovascular risk and prevention · 2023Article
- Oral Drug Absorption and Drug Disposition in Critically Ill Cardiac Patients.Pharmaceutics · 2023Article
- Use of Clearance Concepts to Simulate Impact of Interleukin-6 on Drug Elimination Governed by Cytochromes P450 3A4 and Glomerular Filtration Rate.European journal of drug metabolism and pharmacokinetics · 2023Article
- Therapeutic Drug Monitoring of Tyrosine Kinase Inhibitors in the Treatment of Advanced Renal Cancer.Cancers · 2023Review
- Exposure-Response Analysis of Osimertinib in Patients with Advanced Non-Small-Cell Lung Cancer.Pharmaceutics · 2022Article
- Impact of polymorphisms of pharmacokinetics-related genes and the inflammatory response on the metabolism of voriconazole.Pharmacology research & perspectives · 2022Article
- PBPK Modelling of Dexamethasone in Patients With COVID-19 and Liver Disease.Frontiers in pharmacology · 2022Article
- Association between Olaparib Exposure and Early Toxicity in BRCA-Mutated Ovarian Cancer Patients: Results from a Retrospective Multicenter Study.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Influence of Inflammation on Cytochromes P450 Activity in Adults: A Systematic Review of the Literature.Frontiers in pharmacology · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeFor decades, inflammation has been considered a cause of pharmacokinetic variability, mainly in relation to the inhibitory effect of pro-inflammatory cytokines on the expression level and activity of cytochrome P450 (CYP). In vitro and clinical studies have shown that two major CYPs, CYP2C19 and CYP3A4, are both impaired. The objective of the present study was to quantify the impact of the inflammatory response on the activity of both CYPs in order to predict the pharmacokinetic profile of their substrates according to systemic C-reactive protein (CRP).
methodsThe relationships between CRP concentration and both CYPs activities were estimated and validated using clinical data first on midazolam then on voriconazole. Finally, clinical data on omeprazole were used to validate the findings. For each substrate, a physiologically based pharmacokinetics model was built using a bottom-up approach, and the relationships between CRP level and CYP activities were estimated by a top-down approach. After incorporating the respective relationships, we compared the predictions and observed drug concentrations.
resultsChanges in pharmacokinetic profiles and parameters induced by inflammation seem to be captured accurately by the models.
conclusionsThese findings suggest that the pharmacokinetics of CYP2C19 and CYP3A4 substrates can be predicted depending on the CRP concentration.
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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 Socratic graph.