ArticleCPT: pharmacometrics & systems pharmacology2020
Mechanistic Models as Framework for Understanding Biomarker Disposition: Prediction of Creatinine-Drug Interactions.
Article in CPT: pharmacometrics & systems pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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
14 citing papers in PubMed, 28 citations in OpenAlex.
- Population pharmacokinetic modeling and simulation to support qualification of pyridoxic acid as endogenous biomarker of OAT1/3 renal transporters.CPT: pharmacometrics & systems pharmacology · 2021Trial
- Enhancing therapeutic strategies and drug development for patients with kidney disease.Expert opinion on drug safety · 2026Review
- Predicting OCT2/MATEs-Mediated Drug Interactions in Healthy Volunteers and Patients with Chronic Kidney Disease: Insights from Extended Clearance Concept, Endogenous Biomarkers, and In Vitro Inhibition Studies (Perspectives from the International Transporter Consortium).Clinical pharmacology and therapeutics · 2025Review
- Drug Interaction PBPK Modeling: Review of the Literature Exposes the Need for Increased Verification of Model Inputs and Outputs as Part of Credibility Assessment.Clinical and translational science · 2025Review
- Effect of Pseudonephrotoxicity on Apparent Acute Kidney Injury Incidence and Severity: A Simulation Study.Clinical journal of the American Society of Nephrology : CJASN · 2024Article
- Utilising Endogenous Biomarkers in Drug Development to Streamline the Assessment of Drug-Drug Interactions Mediated by Renal Transporters: A Pharmaceutical Industry Perspective.Clinical pharmacokinetics · 2024Review
- Membrane transporters in drug development and as determinants of precision medicine.Nature reviews. Drug discovery · 2024Review
- Use of In Vivo Imaging and Physiologically-Based Kinetic Modelling to Predict Hepatic Transporter Mediated Drug-Drug Interactions in Rats.Pharmaceutics · 2023Article
- The Interplay between Uremic Toxins and Albumin, Membrane Transporters and Drug Interaction.Toxins · 2022Review
- Membrane Carriers and Transporters in Kidney Physiology and Disease.Biomedicines · 2021Review
- Does "Birth" as an Event Impact Maturation Trajectory of Renal Clearance via Glomerular Filtration? Reexamining Data in Preterm and Full-Term Neonates by Avoiding the Creatinine Bias.Journal of clinical pharmacology · 2021Article
- Physiologically-Based Pharmacokinetic Modelling of Creatinine-Drug Interactions in the Chronic Kidney Disease Population.CPT: pharmacometrics & systems pharmacology · 2020Article
- Organic Cation Transporters in Human Physiology, Pharmacology, and Toxicology.International journal of molecular sciences · 2020Review
- A Novel Physiologically Based Model of Creatinine Renal Disposition to Integrate Current Knowledge of Systems Parameters and Clinical Observations.CPT: pharmacometrics & systems pharmacology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Creatinine is widely used as a biomarker of glomerular filtration, and, hence, renal function. However, transporter-mediated secretion also contributes to its renal clearance, albeit to a lesser degree. Inhibition of these transporters causes transient serum creatinine elevation, which can be mistaken as impaired renal function. The current study developed mechanistic models of creatinine kinetics within physiologically based framework accounting for multiple transporters involved in creatinine renal elimination, assuming either unidirectional or bidirectional-OCT2 transport (driven by electrochemical gradient). Robustness of creatinine models was assessed by predicting creatinine-drug interactions with 10 perpetrators; performance evaluation accounted for 5% intra-individual variability in serum creatinine. Models showed comparable predictive performances of the maximum steady-state effect regardless of OCT2 directionality assumptions. However, only the bidirectional-OCT2 model successfully predicted the minimal effect of ranitidine. The dynamic nature of models provides clear advantage to static approaches and most advanced framework for evaluating interplay between multiple processes in creatinine renal disposition.
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What Socratic holds
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 Socratic graph.