ArticleCPT: pharmacometrics & systems pharmacology2013
Effect of Ritonavir on (99m)Technetium-Mebrofenin Disposition in Humans: A Semi-PBPK Modeling and In Vitro Approach to Predict Transporter-Mediated DDIs.
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. It is linked to trial NCT02235233 (Clinical Study to Investigate the Effect of NASH), which is not on this map. Cited by 24 papers.
What it found
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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.
Clinical Study to Investigate the Effect of NASH (Non-alcoholic Steatohepatitis) on the Disposition of 99mTechnetium(Tc)-Mebrofenin in Healthy Subjects Compared to Patients With NASH.
Who cites it
24 citing papers in PubMed, 44 citations in OpenAlex.
- Positron Emission Tomography Imaging of [Clinical pharmacology and therapeutics · 2019Trial
- Co-Treatment with Ritonavir or Sertraline Enhances Itraconazole Efficacy Against Azole-ResistantJournal of fungi (Basel, Switzerland) · 2025Article
- Membrane transporters in drug development and as determinants of precision medicine.Nature reviews. Drug discovery · 2024Review
- Physiologically based radiopharmacokinetic (PBRPK) modeling to simulate and analyze radiopharmaceutical therapies: studies of non-linearities, multi-bolus injections, and albumin binding.EJNMMI radiopharmacy and chemistry · 2024Article
- Use of In Vivo Imaging and Physiologically-Based Kinetic Modelling to Predict Hepatic Transporter Mediated Drug-Drug Interactions in Rats.Pharmaceutics · 2023Article
- Predicting disruptions to drug pharmacokinetics and the risk of adverse drug reactions in non-alcoholic steatohepatitis patients.Acta pharmaceutica Sinica. B · 2023Review
- The current status and future prospects for molecular imaging-guided precision surgery.Cancer imaging : the official publication of the International Cancer Imaging Society · 2022Review
- Pharmacokinetic Imaging UsingPharmaceuticals (Basel, Switzerland) · 2022Article
- Current use and future potential of (physiologically based) pharmacokinetic modelling of radiopharmaceuticals: a review.Theranostics · 2022Review
- Physiologically Based Pharmacokinetic Modeling of Transporter-Mediated Hepatic Disposition of Imaging Biomarker Gadoxetate in Rats.Molecular pharmaceutics · 2021Article
- Quantitative Prediction of Interactions Mediated by Transporters and Cytochromes: Application to Organic Anion Transporting Polypeptides, Breast Cancer Resistance Protein and Cytochrome 2C8.Clinical pharmacokinetics · 2020Article
- Use of imaging to assess the activity of hepatic transporters.Expert opinion on drug metabolism & toxicology · 2020Review
- Evaluation of Drug Biliary Excretion Using Sandwich-Cultured Human Hepatocytes.European journal of drug metabolism and pharmacokinetics · 2019Review
- Advancing Predictions of Tissue and Intracellular Drug Concentrations Using In Vitro, Imaging and Physiologically Based Pharmacokinetic Modeling Approaches.Clinical pharmacology and therapeutics · 2018Article
- Influence of OATPs on Hepatic Disposition of Erlotinib Measured With Positron Emission Tomography.Clinical pharmacology and therapeutics · 2018Article
- Transporter-Mediated Alterations in Patients With NASH Increase Systemic and Hepatic Exposure to an OATP and MRP2 Substrate.Clinical pharmacology and therapeutics · 2017Article
- Prediction of Hepatic Efflux Transporter-Mediated Drug Interactions: When Is it Optimal to Measure Intracellular Unbound Fraction of Inhibitors?Journal of pharmaceutical sciences · 2017Article
- Prediction of Altered Bile Acid Disposition Due to Inhibition of Multiple Transporters: An Integrated Approach Using Sandwich-Cultured Hepatocytes, Mechanistic Modeling, and Simulation.The Journal of pharmacology and experimental therapeutics · 2016Article
- Sandwich-Cultured Hepatocytes as a Tool to Study Drug Disposition and Drug-Induced Liver Injury.Journal of pharmaceutical sciences · 2016Review
- Altered morphine glucuronide and bile acid disposition in patients with nonalcoholic steatohepatitis.Clinical pharmacology and therapeutics · 2015Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
A semiphysiologically based pharmacokinetic (semi-PBPK) model was developed to describe a unique blood, liver, and bile clinical data set for the hepatobiliary imaging agent (99m)Technetium-mebrofenin ((99m)Tc-mebrofenin), and to simulate sites/mechanisms of a (99m)Tc-mebrofenin-ritonavir drug-drug interaction (DDI). The transport inhibitor ritonavir (multiple-dose: 2 × 300 mg) significantly increased systemic (99m)Tc-mebrofenin exposure as compared with control (4,464 ± 1,861 vs. 1,970 ± 311 nCi min/ml; mean ± SD), without affecting overall hepatic exposure or biliary recovery. A novel extrahepatic distribution compartment was required to characterize (99m)Tc-mebrofenin disposition. Ritonavir inhibited (99m)Tc-mebrofenin accumulation in human sandwich-cultured hepatocytes (SCH) (half maximal inhibitory concentration (IC50) = 3.46 ± 1.53 µmol/l). Despite ritonavir accumulation in hepatocytes, intracellular binding was extensive (97. 6%), which limited interactions with multidrug resistance protein 2 (MRP2)-mediated biliary excretion. These in vitro data supported conclusions from modeling/simulation that ritonavir inhibited (99m)Tc-mebrofenin hepatic uptake, but not biliary excretion, at clinically relevant concentrations. This integrated approach, utilizing modeling, clinical, and in vitro data, emphasizes the importance of hepatic and extrahepatic distribution, assessment of inhibitory potential in relevant in vitro systems, and intracellular unbound concentrations to assess transporter-mediated hepatic DDIs.CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e20; doi:10.1038/psp.2012.21; advance online publication 2 January 2013.
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.