ArticleCPT: pharmacometrics & systems pharmacology2026
Impact of Obesity and MASH on Zonal Hepatocellular Statin Exposure: Pharmacodynamic Insights From a Permeability-Limited Multicompartment Liver Model.
Article in CPT: pharmacometrics & systems pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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.
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Who cites it
1 citing paper in PubMed.
- Impact of Obesity and MASH on Zonal Hepatocellular Statin Exposure: Pharmacodynamic Insights From a Permeability-Limited Multicompartment Liver Model.CPT: pharmacometrics & systems pharmacology · 2026Article
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Authors and funding
6 authors.
Funding
Abstract
Statins are frequently prescribed for hyperlipidemia, a common comorbidity in patients with obesity and/or metabolic dysfunction-associated steatohepatitis (MASH). However, limited knowledge exists on how MASH may alter statin disposition within hepatocytes where the statin target, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, is located. This study used a physiologically based pharmacokinetic (PBPK)/permeability-limited multicompartment liver (PerMCL) framework, incorporating zonal transporter and drug-metabolizing enzyme data. Systemic and hepatocellular concentrations of pravastatin, rosuvastatin, and atorvastatin were simulated in Healthy Volunteers (HV), Obese, Morbidly Obese, and MASH virtual populations with the Simcyp Simulator. A pharmacodynamic model in Simcyp Designer was then used to simulate alterations in rosuvastatin cholesterol-lowering efficacy between these populations. Hepatic transport and metabolism pathways were verified against clinical data. Organic anion transporting polypeptide (OATP)1B model uptake pathways were verified using genotype and drug-drug interaction data. Atorvastatin metabolism pathways were verified using metabolite data. Steady-state plasma and zonal hepatocellular concentration-time profiles for each statin were simulated across virtual populations of 100 individuals aged 40-65 years. Simulations predicted > 70% increases in maximal total plasma concentrations and area under the curve for pravastatin and rosuvastatin in MASH compared to HV, with changes in these parameters for atorvastatin simulated to increase > 250%. In MASH, unbound hepatocellular exposure increased by up to 127% in the periportal region for atorvastatin and decreased by up to 55% in the pericentral region for rosuvastatin. The pharmacodynamic model simulated decreased rosuvastatin cholesterol-lowering efficacy in MASH compared with Obese, which could be compensated for with a 50% increase in dose according to exploratory simulations.
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Registered trials
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