ArticleDrug metabolism and disposition: the biological fate of chemicals2009
Relationship between drug/metabolite exposure and impairment of excretory transport function.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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.
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Who cites it
23 citing papers in PubMed.
- Pitavastatin is a more sensitive and selective organic anion-transporting polypeptide 1B clinical probe than rosuvastatin.British journal of clinical pharmacology · 2014Trial
- A 3-step static mechanistic modeling approach to predicting transporter- and enzyme-mediated interaction signals of direct oral anticoagulants.Drug metabolism and disposition: the biological fate of chemicals · 2026Article
- 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
- Assessing the Functional Redundancy between P-gp and BCRP in Controlling the Brain Distribution and Biliary Excretion of Dual Substrates with PET Imaging in Mice.Pharmaceutics · 2021Article
- Physiologically Based Pharmacokinetic Modeling of Central Nervous System Pharmacokinetics of CDK4/6 Inhibitors to Guide Selection of Drug and Dosing Regimen for Brain Cancer Treatment.Clinical pharmacology and therapeutics · 2021Article
- Protein Expression and Functional Relevance of Efflux and Uptake Drug Transporters at the Blood-Brain Barrier of Human Brain and Glioblastoma.Clinical pharmacology and therapeutics · 2020Article
- Mechanistic Modeling of the Hepatic Disposition of Estradiol-17Drug metabolism and disposition: the biological fate of chemicals · 2020Article
- Cellular Pharmacokinetic Model-Based Analysis of Genistein, Glyceollin, and MK-571 Effects on 5 (and 6)-Carboxy-2',7'-Dichloroflourescein Disposition in Caco-2 Cells.Journal of pharmaceutical sciences · 2018Article
- Physiologically Based Pharmacokinetic Modeling of Transporter-Mediated Hepatic Clearance and Liver Partitioning of OATP and OCT Substrates in Cynomolgus Monkeys.The AAPS journal · 2017Article
- A Comprehensive Review of Drug-Drug Interactions with Metformin.Clinical pharmacokinetics · 2015Review
- Brain and Testis Accumulation of Regorafenib is Restricted by Breast Cancer Resistance Protein (BCRP/ABCG2) and P-glycoprotein (P-GP/ABCB1).Pharmaceutical research · 2015Article
- Species differences in hepatobiliary disposition of taurocholic acid in human and rat sandwich-cultured hepatocytes: implications for drug-induced liver injury.The Journal of pharmacology and experimental therapeutics · 2015Article
- Prediction of pharmacokinetics and drug-drug interactions when hepatic transporters are involved.Clinical pharmacokinetics · 2014Review
- An experimental approach to evaluate the impact of impaired transport function on hepatobiliary drug disposition using Mrp2-deficient TR- rat sandwich-cultured hepatocytes in combination with Bcrp knockdown.Molecular pharmaceutics · 2014Article
- Predicting the outer boundaries of P-glycoprotein (P-gp)-based drug interactions at the human blood-brain barrier based on rat studies.Molecular pharmaceutics · 2014Article
- Utility of Oatp1a/1b-knockout and OATP1B1/3-humanized mice in the study of OATP-mediated pharmacokinetics and tissue distribution: case studies with pravastatin, atorvastatin, simvastatin, and carboxydichlorofluorescein.Drug metabolism and disposition: the biological fate of chemicals · 2014Article
- Hepatic basolateral efflux contributes significantly to rosuvastatin disposition II: characterization of hepatic elimination by basolateral, biliary, and metabolic clearance pathways in rat isolated perfused liver.The Journal of pharmacology and experimental therapeutics · 2013Article
- Trimethoprim-metformin interaction and its genetic modulation by OCT2 and MATE1 transporters.British journal of clinical pharmacology · 2013Article
- Intracellular drug concentrations and transporters: measurement, modeling, and implications for the liver.Clinical pharmacology and therapeutics · 2013Review
- ITC recommendations for transporter kinetic parameter estimation and translational modeling of transport-mediated PK and DDIs in humans.Clinical pharmacology and therapeutics · 2013Review
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
The quantitative impact of excretory transport modulation on the systemic exposure to xenobiotics and derived metabolites is poorly understood. This article presents fundamental relationships between exposure and loss of a specific excretory process that contributes to overall clearance. The mathematical relationships presented herein were explored on the basis of hepatic excretory data for polar metabolites formed in the livers of various transporter-deficient rodents. Experimental data and theoretical relationships indicated that the fold change in exposure is governed by the relationship, 1/(1 - f(e)), where f(e) is the fraction excreted by a particular transport protein. Loss of function of a transport pathway associated with f(e) < 0.5 will have minor consequences (<2-fold) on exposure, but exposure will increase exponentially in response to loss of function of transport pathways with f(e) > 0.5. These mathematical relationships may be extended to other organs, such as the intestine and kidney, as well as to systemic drug exposure. Finally, the relationship between exposure and f(e) is not only applicable to complete loss of function of a transport pathway but also can be extended to partial inhibition scenarios by modifying the equation with the ratio of the inhibitor concentration and inhibition constant.
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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.