Results 211 to 220 of about 111,693 (253)

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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Evaluation of the human prediction of clearance from hepatocyte and microsome intrinsic clearance for 52 drug compounds

Xenobiotica, 2010
We compare three different approaches to scale clearance (CL) from human hepatocyte and microsome CL(int) (intrinsic CL) for 52 drug compounds. By using the well-stirred model with protein binding included only 11% and 30% of the compounds were predicted within 2-fold and the average absolute fold errors (AAFE) for the predictions were 5.9 and 4.1 for ...
A-K, Sohlenius-Sternbeck, L, Afzelius, P, Prusis, J, Neelissen, J, Hoogstraate, J, Johansson, E, Floby, A, Bengtsson, O, Gissberg, J, Sternbeck, C, Petersson   +10 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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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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Development of an in vitro incubation procedure for screening of CYP2D6 intrinsic clearance

Journal of Chromatography B, 2007
The in vitro intrinsic clearances (CL(int)) for the metabolism of p-methoxymethamphetamine (PMMA) and fluoxetine by the CYP2D6 enzyme were calculated using a steady-state (SS) approach and a new general enzyme (GE) method, which measures the formation of product and the depletion of substrate as a function of time.
Sarah E G, Porter, Richard B, Keithley, Sarah C, Rutan   +2 more
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Clearance of 5-hydroxytryptamine by rat lung and liver: the importance of relative perfusion and intrinsic clearance.

The Journal of Pharmacology and Experimental Therapeutics, 1980
Since it is replete with degradative enzymes, the liver is commonly viewed as the organ primarily responsible for clearing circulating substances which are eliminated by metabolism. However, the enzyme content of an organ is not the only determinant of clearance.
D A, Wiersma, R A, Roth
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The Impact of Reference Data Selection for the Prediction Accuracy of Intrinsic Hepatic Metabolic Clearance

Journal of Pharmaceutical Sciences, 2022
In vitro-in vivo prediction results for hepatic metabolic clearance (CLH) and intrinsic CLH (CLint) vary widely among studies. Reasons are not fully investigated and understood. The possibility to select favorable reference data for in vivo CLH and CLint and unbound fraction in plasma (fu) is among possible explanations.
Urban Fagerholm, Ola Spjuth, Sven Hellberg   +2 more
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DIRECT DETERMINATION OF UNBOUND INTRINSIC DRUG CLEARANCE IN THE MICROSOMAL STABILITY ASSAY

Drug Metabolism and Disposition, 2005
The microsomal stability assay is commonly used to rank compounds according to their metabolic stability. Determination of the unbound intrinsic clearance (CL(in,u)) is essential for the accurate comparison of compounds, since nonspecific binding to microsomes can lead to an underestimation of the microsomal clearance.
Claudio, Giuliano, Mark, Jairaj, Christian M, Zafiu, Ralph, Laufer   +3 more
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Scaling of antipyrine intrinsic clearance of unbound drug in 15 mammalian species

European Journal of Drug Metabolism and Pharmacokinetics, 1984
The intrinsic clearance of unbound drug (CLuint) for antipyrine in 15 mammalian species was characterized by an equation of the form, CLuint = theta 1 (body weight) theta 2 (brain weight) theta 3, where thetas are constants. Maximum lifespan potential in mammals can also be characterized by an equation of this form.
H, Boxenbaum, J B, Fertig
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A UNIFIED MODEL FOR PREDICTING HUMAN HEPATIC, METABOLIC CLEARANCE FROM IN VITRO INTRINSIC CLEARANCE DATA IN HEPATOCYTES AND MICROSOMES

Drug Metabolism and Disposition, 2005
The aim of this study was to evaluate a unified method for predicting human in vivo intrinsic clearance (CL(int, in vivo)) and hepatic clearance (CL(h)) from in vitro data in hepatocytes and microsomes by applying the unbound fraction in blood (fu(b)) and in vitro incubations (fu(inc)).
Robert J, Riley, D F, McGinnity, R P, Austin   +2 more
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