ArticleClinical pharmacology and therapeutics2019
Use of Physiologically Based Pharmacokinetic Modeling to Evaluate the Effect of Chronic Kidney Disease on the Disposition of Hepatic CYP2C8 and OATP1B Drug Substrates.
Article in Clinical pharmacology and therapeutics, 2019. 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.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Utilization of Pharmacokinetic/Pharmacodynamic Modeling in Pharmacoepidemiological Studies: A Systematic Review on Antiarrhythmic and Glucose-Lowering Medicines.Frontiers in pharmacology · 2022Pooled it
- From Population-Based PBPK to Individualized Virtual Twins: Clinical Validation and Applications in Medicine.Journal of clinical medicine · 2026Review
- Applications of PBPK Modeling to Estimate Drug Metabolism and Related ADME Processes in Specific Populations.Pharmaceutics · 2025Review
- Development of PBPK Population Model for End-Stage Renal Disease Patients to Inform OATP1B-, BCRP-, P-gp-, and CYP3A4-Mediated Drug Disposition with Individual Influencing Factors.Pharmaceutics · 2025Article
- Leveraging In Silico and Artificial Intelligence Models to Advance Drug Disposition and Response Predictions Across the Lifespan.Clinical and translational science · 2025Review
- Microdose Cocktail Study Reveals the Activity and Key Influencing Factors of OATP1B, P-Gp, BCRP, and CYP3A in End-Stage Renal Disease Patients.Clinical pharmacology and therapeutics · 2025Article
- Membrane transporters in drug development and as determinants of precision medicine.Nature reviews. Drug discovery · 2024Review
- Physiologically based pharmacokinetic (PBPK) modeling of pitavastatin in relation to SLCO1B1 genetic polymorphism.Archives of pharmacal research · 2024Article
- Use of physiologically-based pharmacokinetic modeling to understand the effect of omeprazole administration on the pharmacokinetics of oral extended-release nifedipine.CPT: pharmacometrics & systems pharmacology · 2024Article
- Physiologically Based Pharmacokinetic Modelling to Predict Imatinib Exposures in Cancer Patients with Renal Dysfunction: A Case Study.Pharmaceutics · 2023Article
- Single-dose Pharmacokinetics of Eluxadoline in Healthy Participants With Normal Renal Function and Participants With Renal Impairment.Clinical pharmacology in drug development · 2023Article
- Article
- Effect of Chronic Kidney Disease on the Renal Secretion via Organic Anion Transporters 1/3: Implications for Physiologically-Based Pharmacokinetic Modeling and Dose Adjustment.Clinical pharmacology and therapeutics · 2022Article
- Coproporphyrin I as an Endogenous Biomarker to Detect Reduced OATP1B Activity and Shift in Elimination Route in Chronic Kidney Disease.Clinical pharmacology and therapeutics · 2022Article
- Use of Physiologically Based Pharmacokinetic Modeling to Evaluate the Impact of Chronic Kidney Disease on CYP3A4-Mediated Metabolism of Saxagliptin.Journal of clinical pharmacology · 2022Article
- Applications, Challenges, and Outlook for PBPK Modeling and Simulation: A Regulatory, Industrial and Academic Perspective.Pharmaceutical research · 2022Review
- Quantitative Proteomics in Translational Absorption, Distribution, Metabolism, and Excretion and Precision Medicine.Pharmacological reviews · 2022Review
- Determining the Effects of Chronic Kidney Disease on Organic Anion Transporter1/3 Activity Through Physiologically Based Pharmacokinetic Modeling.Clinical pharmacokinetics · 2022Article
- Population Pharmacokinetic Modelling for Nifedipine to Evaluate the Effect of Parathyroid Hormone on CYP3A in Patients with Chronic Kidney Disease.Drug design, development and therapy · 2022Article
- Application of a Physiologically Based Pharmacokinetic Approach to Predict Theophylline Pharmacokinetics Using Virtual Non-Pregnant, Pregnant, Fetal, Breast-Feeding, and Neonatal Populations.Frontiers in pediatrics · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 7 institutions in 3 countries.
Funding
Abstract
Chronic kidney disease (CKD) differentially affects the pharmacokinetics (PK) of nonrenally cleared drugs via certain pathways (e.g., cytochrome P450 (CYP)2D6); however, the effect on CYP2C8-mediated clearance is not well understood because of overlapping substrate specificity with hepatic organic anion-transporting polypeptides (OATPs). This study used physiologically based pharmacokinetic (PBPK) modeling to delineate potential changes in CYP2C8 or OATP1B activity in patients with CKD. Drugs analyzed are predominantly substrates of CYP2C8 (rosiglitazone and pioglitazone), OATP1B (pitavastatin), or both (repaglinide). Following initial model verification, pharmacokinetics (PK) of these drugs were simulated in patients with severe CKD considering changes in glomerular filtration rate (GFR), plasma protein binding, and activity of either CYP2C8 and/or OATP1B in a stepwise manner. The PBPK analysis suggests that OATP1B activity could be decreased up to 60% in severe CKD, whereas changes to CYP2C8 are negligible. This improved understanding of CKD effect on clearance pathways could be important to inform the optimal use of nonrenally eliminated drugs in patients with CKD.
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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.