Organic Anion–Transporting Polypeptide and Efflux Transporter–Mediated Hepatic Uptake and Biliary Excretion of Cilostazol and Its Metabolites in Rats and Humans

Wang, Chong; Huo, Xiaokui; Wang, Changyuan; Meng, Qiang; Liu, Zhihao; Sun, Pengyuan; Cang, Jian; Sun, Huijun; Liu, Kexin

doi:10.1016/j.xphs.2017.05.011

Cited by 4 publications

(1 citation statement)

References 38 publications

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“…Transporters also affect the tissue distribution and contribute to the selective distribution of drugs to specific tissues. For example, OATP1B1 and OATP1B3 are the major uptake transporters in the liver for cilostazol, and MRP2, BCRP, P-gp pump cilostazol out of the liver into bile 86 . These transporters assist the liver-specific distribution of cilostazol.…”

Section: Determinants Of Pkmentioning

confidence: 99%

Current trends in drug metabolism and pharmacokinetics

Meng

Yang

et al. 2019

Acta Pharmaceutica Sinica B

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188

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Pharmacokinetics (PK) is the study of the absorption, distribution, metabolism, and excretion (ADME) processes of a drug. Understanding PK properties is essential for drug development and precision medication. In this review we provided an overview of recent research on PK with focus on the following aspects: (1) an update on drug-metabolizing enzymes and transporters in the determination of PK, as well as advances in xenobiotic receptors and noncoding RNAs (ncRNAs) in the modulation of PK, providing new understanding of the transcriptional and posttranscriptional regulatory mechanisms that result in inter-individual variations in pharmacotherapy; (2) current status and trends in assessing drug–drug interactions, especially interactions between drugs and herbs, between drugs and therapeutic biologics, and microbiota-mediated interactions; (3) advances in understanding the effects of diseases on PK, particularly changes in metabolizing enzymes and transporters with disease progression; (4) trends in mathematical modeling including physiologically-based PK modeling and novel animal models such as CRISPR/Cas9-based animal models for DMPK studies; (5) emerging non-classical xenobiotic metabolic pathways and the involvement of novel metabolic enzymes, especially non-P450s. Existing challenges and perspectives on future directions are discussed, and may stimulate the development of new research models, technologies, and strategies towards the development of better drugs and improved clinical practice.

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Section: Determinants Of Pkmentioning

confidence: 99%

Current trends in drug metabolism and pharmacokinetics

Meng

Yang

et al. 2019

Acta Pharmaceutica Sinica B

Self Cite

188

124

View full text Add to dashboard Cite

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Quantitative prediction of breast cancer resistant protein mediated drug‐drug interactions using physiologically‐based pharmacokinetic modeling

Costales

Lin

Kimoto

et al. 2021

CPT Pharmacom & Syst Pharma

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Predictive Modeling of HMG-CoA Reductase Inhibitory Activity and Design of New HMG-CoA Reductase Inhibitors

Samizo

Kaneko

2023

ACS Omega

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As blood cholesterol increases, it accumulates in the intima of blood vessels, elevating the risk of atherosclerosis and coronary artery disease. Drugs that inhibit enzymes essential for cholesterol synthesis are effective in improving blood cholesterol levels. Statins are used to treat hypercholesterolemia as they inhibit 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMGR), the rate-limiting enzyme in cholesterol synthesis. Statins are known to exert their effects by translocating to the liver, where they are taken up by the organic anion transporting polypeptide 1B1 (OATP1B1). Therefore, we hypothesized that a compound with high HMGR inhibitory activity and high affinity for OATP1B1 would be an excellent new therapeutic agent for hypercholesterolemia with increased liver selectivity and fewer side effects. In this study, we developed two models for predicting HMGR inhibitory activity and OATP1B1 affinity to propose the chemical structure of a new therapeutic agent for hypercholesterolemia with both high inhibitory activity and high liver selectivity. HMGR inhibitory activity and OATP1B1 affinity prediction models were constructed with high prediction accuracy for the test data: r 2 = 0.772 and 0.768, respectively. New chemical structures were then input into these models to search for candidate compounds. We found compounds with higher HMGR inhibitory activity and OATP1B1 affinity than rosuvastatin, the most recently developed statin drug, and compounds that did not have a common structure of statins with high HMGR inhibitory activity.

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Organic Anion–Transporting Polypeptide and Efflux Transporter–Mediated Hepatic Uptake and Biliary Excretion of Cilostazol and Its Metabolites in Rats and Humans

Cited by 4 publications

References 38 publications

Current trends in drug metabolism and pharmacokinetics

Current trends in drug metabolism and pharmacokinetics

Quantitative prediction of breast cancer resistant protein mediated drug‐drug interactions using physiologically‐based pharmacokinetic modeling

Predictive Modeling of HMG-CoA Reductase Inhibitory Activity and Design of New HMG-CoA Reductase Inhibitors

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