Results 201 to 210 of about 103,612 (260)

Use of intrinsic clearance for prediction of human hepatic clearance

Expert Opinion on Drug Metabolism & Toxicology, 2010
The use of intrinsic metabolic stability/clearance and other in vitro pharmacokinetic data for the selection of drug candidates for clinical evaluation during discovery lead optimization has become one of the primary focuses of research organizations involved in new drug discovery.
Piyun, Chao, Annette S, Uss, K C, Cheng
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Prediction of hepatic microsomal intrinsic clearance and human clearance values for drugs

Journal of Molecular Graphics and Modelling, 2009
Twenty-nine drugs of different structures were used in theoretical QSAR analysis of human hepatic microsomal intrinsic clearance (in vitro T(1/2) and in vitro CL'(int)) and whole body clearance (CL(blood)). The examined compounds demonstrated a wide range of scaled intrinsic clearance values. Constitutional, geometrical, physico-chemical and electronic
Nikolić, Katarina, Agbaba, Danica
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Relationship between Passive Permeability, Efflux, and Predictability of Clearance from In Vitro Metabolic Intrinsic Clearance

Drug Metabolism and Disposition, 2010
In vitro intrinsic metabolic clearance (CL(int)) is used routinely for compound selection in drug discovery; however, in vitro CL(int) often underpredicts in vivo clearance (CL). Forty-one proprietary compounds and 16 marketed drugs were selected to determine whether permeability and efflux status could influence the predictability of CL from in vitro ...
Liyue, Huang, Loren, Berry, Sindhura, Ganga, Brett, Janosky, April, Chen, Jonathan, Roberts, Adria E, Colletti, Min-Hwa Jasmine, Lin   +7 more
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Quantitative Translation of Substrate Intrinsic Clearance from Recombinant CYP1A1 to Humans

The AAPS Journal, 2023
CYP1A1 is a cytochrome P450 family 1 enzyme that is mostly expressed in the extrahepatic tissues. To understand the CYP1A1 contribution to drug clearance in humans, we examined the in vitro-in vivo extrapolation (IVIVE) of intrinsic clearance (CLint) for a set of drugs that are in vitro CYP1A1 substrates. Despite being strong in vitro CYP1A1 substrates,
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In Vivo Biliary Clearance Should Be Predicted by Intrinsic Biliary Clearance in Sandwich-Cultured Hepatocytes

Drug Metabolism and Disposition, 2012
It has been reported that in vivo biliary clearance can be predicted using sandwich-cultured rat and human hepatocytes. The predicted apparent biliary clearance (CL(bile, app)) from sandwich- cultured rat hepatocytes (SCRH) based on medium concentrations correlates to in vivo CL(bile, app) based on plasma concentrations of angiotensin II receptor ...
Masanori, Nakakariya, Midori, Ono, Nobuyuki, Amano, Toshiya, Moriwaki, Kazuya, Maeda, Yuichi, Sugiyama   +5 more
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Multispecies Machine Learning Predictions of In Vitro Intrinsic Clearance with Uncertainty Quantification Analyses

Molecular Pharmaceutics, 2022
In pharmaceutical research, compounds are optimized for metabolic stability to avoid a too fast elimination of the drug. Intrinsic clearance (CLint) measured in liver microsomes or hepatocytes is an important parameter during lead optimization. In this work, machine learning models were developed to relate the compound structure to microsomal metabolic
Raquel Rodríguez-Pérez, Markus Trunzer, Nadine Schneider, Bernard Faller, Grégori Gerebtzoff   +4 more
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