ArticleThe Journal of pharmacology and experimental therapeutics2013
Hepatic basolateral efflux contributes significantly to rosuvastatin disposition I: characterization of basolateral versus biliary clearance using a novel protocol in sandwich-cultured hepatocytes.
Article in The Journal of pharmacology and experimental therapeutics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
35 citing papers in PubMed, 96 citations in OpenAlex.
- Positron Emission Tomography Imaging of [Clinical pharmacology and therapeutics · 2019Trial
- Pitavastatin is a more sensitive and selective organic anion-transporting polypeptide 1B clinical probe than rosuvastatin.British journal of clinical pharmacology · 2014Trial
- Evaluation of a human 3D multicellular hepatic spheroid model as a platform for studying hepatic transporters.Cellular and molecular life sciences : CMLS · 2025Article
- Rosuvastatin PBPK Modeling: Incorporating Liver Concentrations and Effects of Ethnicity, Genetic Polymorphisms, Lactone Formation, DDI and Pregnancy.CPT: pharmacometrics & systems pharmacology · 2025Article
- Article
- Physiologically Based Pharmacokinetic (PBPK) Model Predictions of Disease Mediated Changes in Drug Disposition in Patients with Nonalcoholic Fatty Liver Disease (NAFLD).Pharmaceutical research · 2024Article
- Mechanistic Static Model based Prediction of Transporter Substrate Drug-Drug Interactions Utilizing Atorvastatin and Rifampicin.Pharmaceutical research · 2023Article
- 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
- Advancing Estimation of Hepatobiliary Clearances in Physiologically Based Pharmacokinetic Models of Rosuvastatin Using Human Hepatic Concentrations.Pharmaceutical research · 2021Article
- Quantitative prediction of breast cancer resistant protein mediated drug-drug interactions using physiologically-based pharmacokinetic modeling.CPT: pharmacometrics & systems pharmacology · 2021Article
- Examination of Physiologically-Based Pharmacokinetic Models of Rosuvastatin.CPT: pharmacometrics & systems pharmacology · 2021Review
- Pitfalls in Predicting Hepatobiliary Drug Transport Using Human Sandwich-Cultured Hepatocytes.The AAPS journal · 2020Article
- Mechanistic Modeling of the Hepatic Disposition of Estradiol-17Drug metabolism and disposition: the biological fate of chemicals · 2020Article
- Complex DDI by Fenebrutinib and the Use of Transporter Endogenous Biomarkers to Elucidate the Mechanism of DDI.Clinical pharmacology and therapeutics · 2020Article
- Optimization of Canalicular ABC Transporter Function in HuH-7 Cells by Modification of Culture Conditions.Drug metabolism and disposition: the biological fate of chemicals · 2019Article
- Evaluation of Drug Biliary Excretion Using Sandwich-Cultured Human Hepatocytes.European journal of drug metabolism and pharmacokinetics · 2019Review
- Probe Cocktail to Assess Transporter Function in Sandwich-Cultured Human Hepatocytes.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2019Article
- When Does the Rate-Determining Step in the Hepatic Clearance of a Drug Switch from Sinusoidal Uptake to All Hepatobiliary Clearances? Implications for Predicting Drug-Drug Interactions.Drug metabolism and disposition: the biological fate of chemicals · 2018Article
- Farnesoid X Receptor Agonists Obeticholic Acid and Chenodeoxycholic Acid Increase Bile Acid Efflux in Sandwich-Cultured Human Hepatocytes: Functional Evidence and Mechanisms.The Journal of pharmacology and experimental therapeutics · 2018Article
- Effect of Cryopreservation on Enzyme and Transporter Activities in Suspended and Sandwich Cultured Rat Hepatocytes.The AAPS journal · 2018Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Transporters responsible for hepatic uptake and biliary clearance (CLBile) of rosuvastatin (RSV) have been well characterized. However, the contribution of basolateral efflux clearance (CLBL) to hepatic and systemic exposure of RSV is unknown. Additionally, the appropriate design of in vitro hepatocyte efflux experiments to estimate CLBile versus CLBL remains to be established. A novel uptake and efflux protocol was developed in sandwich-cultured hepatocytes (SCH) to achieve desired tight junction modulation while maintaining cell viability. Subsequently, studies were conducted to determine the role of CLBL in the hepatic disposition of RSV using SCH from wild-type (WT) and multidrug resistance-associated protein 2 (Mrp2)-deficient (TR(-)) rats in the absence and presence of the P-glycoprotein and breast cancer resistance protein (Bcrp) inhibitor elacridar (GF120918). RSV CLBile was nearly ablated by GF120918 in TR(-) SCH, confirming that Mrp2 and Bcrp are responsible for the majority of RSV CLBile. Pharmacokinetic modeling revealed that CLBL and CLBile represent alternative elimination routes with quantitatively similar contributions to the overall hepatocellular excretion of RSV in rat SCH under baseline conditions (WT SCH in the absence of GF120918) and also in human SCH. Membrane vesicle experiments revealed that RSV is a substrate of MRP4 (Km = 21 ± 7 µM, Vmax = 1140 ± 210 pmol/min per milligram of protein). Alterations in MRP4-mediated RSV CLBL due to drug-drug interactions, genetic polymorphisms, or disease states may lead to changes in hepatic and systemic exposure of RSV, with implications for the safety and efficacy of this commonly used medication.
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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.