ArticleBiopharmaceutics & drug disposition2016
A physiologically based pharmacokinetic model to predict the pharmacokinetics of highly protein-bound drugs and the impact of errors in plasma protein binding.
Article in Biopharmaceutics & drug disposition, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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
28 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Altered Bioavailability and Pharmacokinetics in Crohn's Disease: Capturing Systems Parameters for PBPK to Assist with Predicting the Fate of Orally Administered Drugs.Clinical pharmacokinetics · 2022Pooled it
- Physiologically Based Pharmacokinetic Modeling to Predict Human Starting Dose and Pharmacokinetics for Rocbrutinib.Clinical and translational science · 2026Article
- Applicability of next-generation risk assessment generic PBK models and their performance within the chemical domain.Archives of toxicology · 2026Article
- An Integrated AIVIVE-PBPK-QIVIVE Framework with HTTK Validation for Probabilistic Risk Assessment of Neodymium Nitrate.Chemical research in toxicology · 2026Article
- Effective Brain Targeting Using the Self-Emulsifying Drug Delivery Systems.AAPS PharmSciTech · 2026Review
- Pharmacokinetic Characteristics of Florfenicol in Freshwater Crocodiles (Animals : an open access journal from MDPI · 2026Article
- Physiologically Based Pharmacokinetic Modeling to Predict Drug-Drug Interactions of Soticlestat as a Victim of CYP Induction and Inhibition, and as a Perpetrator of CYP and P-Glycoprotein Inhibition.Clinical pharmacology in drug development · 2025Article
- Article
- Distribution of quetiapine between serum and whole blood in therapeutic drug-monitoring specimens.Journal of analytical toxicology · 2024Article
- Developing a mechanistic understanding of the nonlinear pharmacokinetics of letermovir and prospective drug interaction with everolimus using physiological-based pharmacokinetic modeling.Clinical and translational science · 2023Article
- Ligand's Partition to the Lipid Bilayer Should Be Accounted for When Estimating Their Affinity to Proteins.Molecules (Basel, Switzerland) · 2023Article
- The Role of "Physiologically Based Pharmacokinetic Model (PBPK)" New Approach Methodology (NAM) in Pharmaceuticals and Environmental Chemical Risk Assessment.International journal of environmental research and public health · 2023Review
- Physiologically Based Pharmacokinetic Modeling Approaches for Patients With SARS-CoV-2 Infection: A Case Study With Imatinib.Journal of clinical pharmacology · 2022Article
- Development and Evaluation of a Physiologically Based Pharmacokinetic Model for Predicting Haloperidol Exposure in Healthy and Disease Populations.Pharmaceutics · 2022Article
- A permeability- and perfusion-based PBPK model for improved prediction of concentration-time profiles.Clinical and translational science · 2022Article
- Using partition analysis as a facile method to derive net clearances.Clinical and translational science · 2022Article
- The blood-to-plasma ratio and predicted GABAForensic toxicology · 2022Article
- IVIVE: Facilitating the Use ofToxics · 2022Review
- A Physiologically Based Pharmacokinetic Model for Predicting Diazepam Pharmacokinetics after Intravenous, Oral, Intranasal, and Rectal Applications.Pharmaceutics · 2021Article
- Camptothecin shows better promise than Curcumin in the inhibition of the Human Telomerase: A computational study.Heliyon · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
Abstract
Predicting the pharmacokinetics of highly protein-bound drugs is difficult. Also, since historical plasma protein binding data were often collected using unbuffered plasma, the resulting inaccurate binding data could contribute to incorrect predictions. This study uses a generic physiologically based pharmacokinetic (PBPK) model to predict human plasma concentration-time profiles for 22 highly protein-bound drugs. Tissue distribution was estimated from in vitro drug lipophilicity data, plasma protein binding and the blood: plasma ratio. Clearance was predicted with a well-stirred liver model. Underestimated hepatic clearance for acidic and neutral compounds was corrected by an empirical scaling factor. Predicted values (pharmacokinetic parameters, plasma concentration-time profile) were compared with observed data to evaluate the model accuracy. Of the 22 drugs, less than a 2-fold error was obtained for the terminal elimination half-life (t1/2 , 100% of drugs), peak plasma concentration (Cmax , 100%), area under the plasma concentration-time curve (AUC0-t , 95.4%), clearance (CLh , 95.4%), mean residence time (MRT, 95.4%) and steady state volume (Vss , 90.9%). The impact of fup errors on CLh and Vss prediction was evaluated. Errors in fup resulted in proportional errors in clearance prediction for low-clearance compounds, and in Vss prediction for high-volume neutral drugs. For high-volume basic drugs, errors in fup did not propagate to errors in Vss prediction. This is due to the cancellation of errors in the calculations for tissue partitioning of basic drugs. Overall, plasma profiles were well simulated with the present PBPK model. Copyright © 2016 John Wiley & Sons, Ltd.
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.