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Membrane transporters in drug development
TLDR
Overall, it is advised that the timing of transporter investigations should be driven by efficacy, safety and clinical trial enrolment questions, as well as a need for further understanding of the absorption, distribution, metabolism and excretion properties of the drug molecule, and information required for drug labelling.
Prediction of pharmacokinetic alterations caused by drug-drug interactions: metabolic interaction in the liver.
Serious side-effects caused by drug interactions have attracted a great deal of attention and have become a social problem since the coadministration of ketoconazole and terfenadine was reported to
Molecular Cloning and Characterization of a New Multispecific Organic Anion Transporter from Rat Brain*
TLDR
A cDNA encoding the new member of the multispecific organic anion transporter family, OAT3, was isolated by the reverse transcription-polymerase chain reaction cloning method and northern blot analysis revealed that rat Oat3 mRNA is expressed in the liver, brain, kidney, and eye.
Contribution of OATP2 (OATP1B1) and OATP8 (OATP1B3) to the Hepatic Uptake of Pitavastatin in Humans
TLDR
OATP2 is the most important transporter for the hepatic uptake of pitavastatin in humans, according to the observed uptake clearance in human hepatocytes, and about 90% of the total hepatic clearance could be accounted for by OATP 2.
Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity,
TLDR
This review encompasses the most important advances in liver functions and hepatotoxicity and analyzes which mechanisms can be studied in vitro and how closely hepatoma, stem cell and iPS cell–derived hepatocyte-like-cells resemble real hepatocytes.
Involvement of Multiple Transporters in the Hepatobiliary Transport of Rosuvastatin
Rosuvastatin is an HMG-CoA reductase inhibitor and one of the most hydrophilic among the commercially available statins. It is efficiently accumulated in the liver and excreted into the bile in an
Gemfibrozil and Its Glucuronide Inhibit the Organic Anion Transporting Polypeptide 2 (OATP2/OATP1B1:SLC21A6)-Mediated Hepatic Uptake and CYP2C8-Mediated Metabolism of Cerivastatin: Analysis of the
TLDR
Considering the possibly concentrated high unbound concentrations of GEM-1-O-glu in the liver and its relatively larger plasma unbound fraction compared with GEM itself, the glucuronide inhibition of the CYP2C8-mediated metabolism of CER appears to be the main mechanism for the clinically relevant drug-drug interaction.
Molecular Cloning and Characterization of Multispecific Organic Anion Transporter 4 Expressed in the Placenta*
TLDR
OAT4 is the first member of the multispecific organic anion transporter family, which is expressed abundantly in the placenta, and might be responsible for the elimination and detoxification of harmful anionic substances from the fetus.
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