Organic Anion Transporting Polypeptide Inhibition Dramatically Increases Plasma Exposure but not Pharmacodynamic Effect nor Inferred Hepatic Intracellular Exposure of Firsocostat

2020 ◽  
Author(s):  
Brian J. Kirby ◽  
Justin D. Lutz ◽  
Mun Sang Yue ◽  
Kimberly L. Garrison ◽  
Ann Ran‐Ran Qin ◽  
...  
Keyword(s):  
Organic Anion ◽  
Pharmacodynamic Effect ◽  
Plasma Exposure ◽  
Organic Anion Transporting Polypeptide

Liver and Statins: A Critical Appraisal of the Evidence

2019 ◽  
Vol 25 (42) ◽  
pp. 5835-5846 ◽  
Author(s):  
Anna Licata ◽  
Antonina Giammanco ◽  
Maria Giovanna Minissale ◽  
Salvatore Pagano ◽  
Salvatore Petta ◽  
...  
Keyword(s):  
Adverse Events ◽  
Association Studies ◽  
Organic Anion ◽  
Genome Wide Association Studies ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Organic Anion Transporting Polypeptide ◽  
Treatment And Prevention ◽  
Genome Wide ◽  
Underlying Mechanisms

Adverse drug reactions (ADRs) represent an important cause of morbidity and mortality worldwide. Statins are a class of drugs whose main adverse effects are drug-induced liver injury (DILI) and myopathy. Some of these may be predictable, due to their pharmacokinetic and pharmacodynamic properties, while others, unfortunately, are idiosyncratic. Genetic factors may also influence patient susceptibility to DILI and myopathy in the case of statins. This review will first discuss the role of statins in cardiovascular disease treatment and prevention and the underlying mechanisms of action. Furthermore, to explore the susceptibility of statin-induced adverse events such as myopathy and hepatotoxicity, it will then focus on the recent Genome-Wide Association Studies (GWAS) concerning the transporter genes, Cytochrome P450 (CYP), organic anion-transporting polypeptide (OATP) and ABCB1 and ABCC1, which seem to play a role in the development of clinically relevant adverse events. Finally, we appraise the evidence for and against the use of statins in metabolic syndrome and in HCV-infected patients, in terms of their safety and efficacy in cardiovascular events.

scholarly journals Minireview: Thyroid Hormone Transporters: The Knowns and the Unknowns

2011 ◽  
Vol 25 (1) ◽  
pp. 1-14 ◽  
Author(s):  
W. Edward Visser ◽  
Edith C. H. Friesema ◽  
Theo J. Visser
Keyword(s):  
Thyroid Hormone ◽  
Organic Anion ◽  
Psychomotor Retardation ◽  
Cellular Level ◽  
Monocarboxylate Transporter ◽  
Causative Role ◽  
Organic Anion Transporting Polypeptide ◽  
Neurological Abnormalities ◽  
Knockout Animals

The effects of thyroid hormone (TH) on development and metabolism are exerted at the cellular level. Metabolism and action of TH take place intracellularly, which require transport of the hormone across the plasma membrane. This process is mediated by TH transporter proteins. Many TH transporters have been identified at the molecular level, although a few are classified as specific TH transporters, including monocarboxylate transporter (MCT)8, MCT10, and organic anion-transporting polypeptide 1C1. The importance of TH transporters for physiology has been illustrated dramatically by the causative role of MCT8 mutations in males with psychomotor retardation and abnormal serum TH concentrations. Although Mct8 knockout animals have provided insight in the mechanisms underlying parts of the endocrine phenotype, they lack obvious neurological abnormalities. Thus, the pathogenesis of the neurological abnormalities in males with MCT8 mutations is not fully understood. The prospects of identifying other transporters and transporter-based syndromes promise an exciting future in the TH transporter field.

scholarly journals Identification of a Novel Human Organic Anion Transporting Polypeptide as a High Affinity Thyroxine Transporter

2002 ◽  
Vol 16 (10) ◽  
pp. 2283-2296 ◽  
Author(s):  
F. Pizzagalli ◽  
B. Hagenbuch ◽  
B. Stieger ◽  
U. Klenk ◽  
G. Folkers ◽  
...  
Keyword(s):  
Organic Anion ◽  
Organic Anion Transporting Polypeptide ◽  
High Affinity

scholarly journals Characterization of Organic Anion Transporting Polypeptide 1b2-null Mice: Essential Role in Hepatic Uptake/Toxicity of Phalloidin and Microcystin-LR

2008 ◽  
Vol 103 (1) ◽  
pp. 35-45 ◽  
Author(s):  
Hong Lu ◽  
Supratim Choudhuri ◽  
Kenichiro Ogura ◽  
Iván L. Csanaky ◽  
Xiaohong Lei ◽  
...  
Keyword(s):  
Essential Role ◽  
Organic Anion ◽  
Hepatic Uptake ◽  
Organic Anion Transporting Polypeptide

scholarly journals Organic Anion Transporting Polypeptide Mediates Organic Anion/HCO3−Exchange

1997 ◽  
Vol 272 (42) ◽  
pp. 26340-26345 ◽  
Author(s):  
Lisa M. Satlin ◽  
Vipul Amin ◽  
Allan W. Wolkoff
Keyword(s):  
Organic Anion ◽  
Organic Anion Transporting Polypeptide
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