Comparison of Methods for Estimating Unbound Intracellular-to-Medium Concentration Ratios in Rat and Human Hepatocytes Using Statins

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Title : Comparison of methods for estimating unbound intracellular - to - medium concentration ratios in rat and human hepatocytes using statins

Supplemental Text: Theoretical derivation of the equations for Kp,uu considering the plasma membrane potential of cells and the fraction of drugs ionized Ccell,unbound and Cmedium are defined as unbound concentrations in cells and in medium, respectively. PSact, PSdif, and CLint are active transport clearance, passive diffusion clearance, and hepatic intrinsic clearance (metabolism + biliary ex...

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Comparison of Methods for Estimating Unbound Intracellular-to-Medium Concentration Ratios in Rat and Human Hepatocytes Using Statins.

It is essential to estimate concentrations of unbound drugs inside the hepatocytes to predict hepatic clearance, efficacy, and toxicity of the drugs. The present study was undertaken to compare predictability of the unbound hepatocyte-to-medium concentration ratios (Kp,uu) by two methods based on the steady-state cell-to-medium total concentration ratios at 37°C and on ice (Kp,uu,ss) and based ...

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ژورنال

عنوان ژورنال: Drug Metabolism and Disposition

سال: 2017

ISSN: 0090-9556,1521-009X

DOI: 10.1124/dmd.116.074823