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- W3139147191 endingPage "3559" @default.
- W3139147191 startingPage "3546" @default.
- W3139147191 abstract "Development of new chemical entities is costly, time-consuming, and has a low success rate. Accurate prediction of pharmacokinetic properties is critical to progress compounds with favorable drug-like characteristics in lead optimization. Of particular importance is the prediction of hepatic clearance, which determines drug exposure and contributes to projection of dose, half-life, and bioavailability. The most commonly employed methodology to predict hepatic clearance is termed in vitro to in vivo extrapolation (IVIVE) that involves measuring drug metabolism in vitro, scaling-up this in vitro intrinsic clearance to a prediction of in vivo intrinsic clearance by reconciling the enzymatic content between the incubation and an average human liver, and applying a model of hepatic disposition to account for limitations of protein binding and blood flow to predict in vivo clearance. This manuscript reviews common in vitro techniques used to predict hepatic clearance as well as current challenges and recent theoretical advancements in IVIVE." @default.
- W3139147191 created "2021-03-29" @default.
- W3139147191 creator A5060581165 @default.
- W3139147191 creator A5075960682 @default.
- W3139147191 date "2021-03-25" @default.
- W3139147191 modified "2023-10-03" @default.
- W3139147191 title "Successful and Unsuccessful Prediction of Human Hepatic Clearance for Lead Optimization" @default.
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