ArticleCPT: pharmacometrics & systems pharmacology2019
Physiologically-Based Pharmacokinetic Modeling of Atorvastatin Incorporating Delayed Gastric Emptying and Acid-to-Lactone Conversion.
Article in CPT: pharmacometrics & systems pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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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.
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Who cites it
22 citing papers in PubMed, 29 citations in OpenAlex.
- Effects of Green Tea Extract on Atorvastatin Pharmacokinetics in Healthy Volunteers.European journal of drug metabolism and pharmacokinetics · 2020Trial
- Impact of Obesity and MASH on Zonal Hepatocellular Statin Exposure: Pharmacodynamic Insights From a Permeability-Limited Multicompartment Liver Model.CPT: pharmacometrics & systems pharmacology · 2026Article
- A Combined Modeling Approach to Predict the Effect of Gastric Emptying Delay on the Pharmacokinetics of Small Molecules.CPT: pharmacometrics & systems pharmacology · 2025Article
- Orally deliverable biomimetic nucleic acid therapies for targeted treatment of atherosclerosis.Acta pharmaceutica Sinica. B · 2025Article
- Determination of the latent geometry of atorvastatin pharmacokinetics by transfer entropy to identify bottlenecks.BMC pharmacology & toxicology · 2025Article
- The Chemical Stability Characterization and Kinetics of Statins in Aqueous Cyclodextrin Ocular Preparations: A Formulation Perspective.Pharmaceutics · 2025Article
- Rat PermQ: A permeability- and perfusion-based physiologically based pharmacokinetic model for improved prediction of drug concentration-time profiles in rat.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- A Comprehensive Review on the Pharmacokinetics and Drug-Drug Interactions of Approved GLP-1 Receptor Agonists and a Dual GLP-1/GIP Receptor Agonist.Drug design, development and therapy · 2025Review
- Multi-omics characterization of type 2 diabetes mellitus-induced gastroenteropathy in the db/db mouse model.Frontiers in cell and developmental biology · 2024Article
- Mechanistic Static Model based Prediction of Transporter Substrate Drug-Drug Interactions Utilizing Atorvastatin and Rifampicin.Pharmaceutical research · 2023Article
- PBPK Modeling of Azithromycin Systemic Exposure in a Roux-en-Y Gastric Bypass Surgery Patient Population.Pharmaceutics · 2023Article
- QiShenYiQi pills, a Chinese patent medicine, increase bioavailability of atorvastatin by inhibiting Mrp2 expression in rats.Pharmaceutical biology · 2022Article
- Population pharmacokinetic of paracetamol and atorvastatin with co-administration of semaglutide.Pharmacology research & perspectives · 2022Article
- Enhancing Atorvastatin In Vivo Oral Bioavailability in the Presence of Inflammatory Bowel Disease and Irritable Bowel Syndrome Using Supercritical Fluid Technology Guided by wbPBPK Modeling in Rat and Human.AAPS PharmSciTech · 2022Article
- In Vitro Assessment of Transporter Mediated Perpetrator DDIs for Several Hepatitis C Virus Direct-Acting Antiviral Drugs and Prediction of DDIs with Statins Using Static Models.The AAPS journal · 2022Article
- Atorvastatin population pharmacokinetics in a real-life setting: Influence of genetic polymorphisms and association with clinical response.Clinical and translational science · 2022Article
- Current Evidence, Challenges, and Opportunities of Physiologically Based Pharmacokinetic Models of Atorvastatin for Decision Making.Pharmaceutics · 2021Review
- Sensitive, High-Throughput Liquid Chromatography-Tandem Mass Spectrometry Analysis of Atorvastatin and Its Pharmacologically Active Metabolites in Serum for Supporting Precision Pharmacotherapy.Molecules (Basel, Switzerland) · 2021Article
- Prediction of Cyclosporin-Mediated Drug Interaction Using Physiologically Based Pharmacokinetic Model Characterizing Interplay of Drug Transporters and Enzymes.International journal of molecular sciences · 2020Article
- The Necessity of Using Changes in Absorption Time to Implicate Intestinal Transporter Involvement in Oral Drug-Drug Interactions.The AAPS journal · 2020Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The drug-drug interaction profile of atorvastatin confirms that disposition is determined by cytochrome P450 (CYP) 3A4 and organic anion transporting polypeptides (OATPs). Drugs that affect gastric emptying, including dulaglutide, also affect atorvastatin pharmacokinetics (PK). Atorvastatin is a carboxylic acid that exists in equilibrium with a lactone form in vivo. The purpose of this work was to assess gastric acid-mediated lactone equilibration of atorvastatin and incorporate this into a physiologically-based PK (PBPK) model to describe atorvastatin acid, lactone, and their major metabolites. In vitro acid-to-lactone conversion was assessed in simulated gastric fluid and included in the model. The PBPK model was verified with in vivo data including CYP3A4 and OATP inhibition studies. Altering the gastric acid-lactone equilibrium reproduced the change in atorvastatin PK observed with dulaglutide. The model emphasizes the need to include gastric acid-lactone conversion and all major atorvastatin-related species for the prediction of atorvastatin PK.
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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 OpenQuestion graph.