Search Results - "MOHUTSKY, Michael A"

Mechanistic understanding of the phase behavior of supersaturated solutions of poorly water-soluble drugs by Tres, Francesco, Posada, Maria M., Hall, Stephen D., Mohutsky, Michael A., Taylor, Lynne S.

“…[Display omitted] Amorphous solid dispersions (ASDs) are a promising formulation strategy to increase both the apparent aqueous solubility and bioavailability…”
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Monitoring the Phase Behavior of Supersaturated Solutions of Poorly Water-Soluble Drugs Using Fluorescence Techniques by Tres, Francesco, Hall, Stephen D, Mohutsky, Michael A, Taylor, Lynne S

“…Phase transformations of poorly water-soluble drugs, in low concentration, supersaturated aqueous solutions are of considerable interest. Herein, fluorescence…”
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Hepatic Organic Anion Transporting Polypeptide-Mediated Clearance in the Beagle Dog: Assessing In Vitro-In Vivo Relationships and Applying Cross-Species Empirical Scaling Factors to Improve Prediction of Human Clearance by Matsunaga, Norikazu, Ufuk, Ayşe, Morse, Bridget L, Bedwell, David W, Bao, Jingqi, Mohutsky, Michael A, Hillgren, Kathleen M, Hall, Stephen D, Houston, J Brian, Galetin, Aleksandra

“…In the present study, the beagle dog was evaluated as a preclinical model to investigate organic anion transporting polypeptide (OATP)-mediated hepatic…”
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The Impact of the Hepatocyte-to-Plasma pH Gradient on the Prediction of Hepatic Clearance and Drug-Drug Interactions for CYP2C9 and CYP3A4 Substrates by Rougée, Luc R A, Mohutsky, Michael A, Bedwell, David W, Ruterbories, Kenneth J, Hall, Stephen D

“…Surrogate assays for drug metabolism and inhibition are traditionally performed in buffer systems at pH 7.4, despite evidence that hepatocyte intracellular pH…”
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Prediction of CYP3A-Mediated Drug-Drug Interactions Using Human Hepatocytes Suspended in Human Plasma by JIALIN MAO, MOHUTSKY, Michael A, HARRELSON, John P, WRIGHTON, Steven A, HALL, Stephen D

“…Cryopreserved human hepatocytes suspended in human plasma (HHSHP) represent an integrated metabolic environment for predicting drug-drug interactions (DDIs)…”
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Potentially increasing the metabolic stability of drug candidates via computational site of metabolism prediction by CYP2C9: The utility of incorporating protein flexibility via an ensemble of structures by Danielson, Matthew L., Desai, Prashant V., Mohutsky, Michael A., Wrighton, Steven A., Lill, Markus A.

“…Cytochrome P450 enzymes are responsible for metabolizing many endogenous and xenobiotic molecules encountered by the human body. It has been estimated that 75%…”
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Apparent high CYP3A5 expression is required for significant metabolism of vincristine by human cryopreserved hepatocytes by Dennison, Jennifer B, Mohutsky, Michael A, Barbuch, Robert J, Wrighton, Steven A, Hall, Stephen D

“…Vincristine is metabolized to one primary metabolite, M1, by cDNA-expressed CYP3A4 and CYP3A5 and by CYP3A enzymes in human liver microsomes. For both systems,…”
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Predictions of the in vivo clearance of drugs from rate of loss using human liver microsomes for phase I and phase II biotransformations by MOHUTSKY, Michael A, CHIEN, Jenny Y, RING, Barbara J, WRIGHTON, Steven A

“…The utility of in vitro metabolism to accurately predict the clearance of hepatically metabolized drugs was evaluated. Three major goals were: (1) to optimize…”
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Structure–Property Relationships and Machine Learning Models for Addressing CYP3A4-Mediated Victim Drug–Drug Interaction Risk in Drug Discovery by Hu, Bingjie, Zhou, Xin, Mohutsky, Michael A, Desai, Prashant V

“…Among the FDA-approved small molecule drugs (2005–2016) that are primarily metabolized by cytochrome P450 (CYP), 64% are primarily metabolized by CYP3A4. As…”
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The Effect of Promiscuous Aggregation on in Vitro Drug Metabolism Assays by Tres, Francesco, Posada, Maria M., Hall, Stephen D., Mohutsky, Michael A., Taylor, Lynne S.

“…Purpose Many bioactive molecules show a type of solution phase behavior, termed promiscuous aggregation, whereby at micromolar concentrations, colloidal…”
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In Vitro and In Vivo Correlation of Hepatic Fraction of Metabolism by P450 in Dogs by Zhou, Xin, Hui, Yu-Hua, Hudson, Loyd, Katyayan, Kishore K, Mohutsky, Michael A, Hao, Junliang, Schober, Douglas A, Hembre, Erik J

“…1-Aminobenzotriazole (ABT) has been widely used as a nonspecific mechanism-based inhibitor of cytochrome P450 (P450) enzymes. It is extensively used in…”
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In vitro characterization of the bioconversion of pomaglumetad methionil, a novel metabotropic glutamate 2/3 receptor agonist peptide prodrug by Moulton, Richard D, Ruterbories, Kenneth J, Bedwell, David W, Mohutsky, Michael A

“…To characterize the hydrolysis of the peptide prodrug pomaglumetad methionil (LY2140023;…”
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Predictions of cytochrome P450-mediated drug-drug interactions using cryopreserved human hepatocytes: comparison of plasma and protein-free media incubation conditions by Mao, Jialin, Mohutsky, Michael A, Harrelson, John P, Wrighton, Steven A, Hall, Stephen D

“…Cryopreserved human hepatocytes suspended in human plasma (HHSHP) have previously provided accurate CYP3A drug-drug interaction (DDI) predictions from a single…”
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Difference in the Pharmacokinetics and Hepatic Metabolism of Antidiabetic Drugs in Zucker Diabetic Fatty and Sprague-Dawley Rats by Zhou, Xin, Rougée, Luc R A, Bedwell, David W, Cramer, Jeff W, Mohutsky, Michael A, Calvert, Nathan A, Moulton, Richard D, Cassidy, Kenneth C, Yumibe, Nathan P, Adams, Lisa A, Ruterbories, Kenneth J

“…The Zucker diabetic fatty (ZDF) rat, an inbred strain of obese Zucker fatty rat, develops early onset of insulin resistance and displays hyperglycemia and…”
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The Impact of the Hepatocyte-to-Plasma pH Gradient on the Prediction of Hepatic Clearance and Drug-Drug Interactions for CYP2D6 Substrates by Rougée, Luc R A, Mohutsky, Michael A, Bedwell, David W, Ruterbories, Kenneth J, Hall, Stephen D

“…The proton gradient from the intracellular space to plasma creates an unbound drug gradient for weak acids and bases that could modulate apparent drug…”
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Investigational small-molecule drug selectively suppresses constitutive CYP2B6 activity at the gene transcription level: physiologically based pharmacokinetic model assessment of clinical drug interaction risk by Zamek-Gliszczynski, Maciej J, Mohutsky, Michael A, Rehmel, Jessica L F, Ke, Alice B

“…The glycogen synthase kinase-3 inhibitor LY2090314 specifically impaired CYP2B6 activity during in vitro evaluation of cytochrome P450 (P450) enzyme induction…”
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THE USE OF A SUBSTRATE CASSETTE STRATEGY TO IMPROVE THE CAPACITY AND THROUGHPUT OF CYTOCHROME P450 INDUCTION STUDIES IN HUMAN HEPATOCYTES by MOHUTSKY, Michael A, PETULLO, David M, WRIGHTON, Steven A

“…The gold standard for estimating the ability of a new chemical entity to induce the human cytochromes P450 (P450s) is to determine the increase in catalytic…”
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Enterohepatic circulation of glucuronide metabolites of drugs in dog by Zhou, Xin, Cassidy, Kenneth C., Hudson, Loyd, Mohutsky, Michael A., Sawada, Geri A., Hao, Junliang

“…The enterohepatic circulation (EHC) of drugs is often the result of the direct glucuronidation, excretion of the metabolite into bile, followed by hydrolysis…”
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Considerations from the IQ induction working group in response to drug–drug interaction guidances from regulatory agencies by Hariparsad, Niresh, Einolf, Heidi, Kenny, Jane, Ramsden, Diane, Buckley, David, Dallas, Shannon, DeKeyser, Joshua Gordon, Palamanda, Jairam, Fung, Conrad, Mohutsky, Michael A., Zhang, George, Balani, Suresh, Chen, Liangfu, Jones, Barry, Sinz, Michael, Siu, Y. Amy, Walsky, Robert Leonard, Tweedie, Donald John

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Hepatic Drug-Metabolizing Enzyme Induction and Implications for Preclinical and Clinical Risk Assessment by Mohutsky, Michael A., Romeike, Annette, Meador, Vince, Lee, William M., Fowler, John, Francke-Carroll, Sabine

“…Hepatic drug metabolizing enzyme (DME) induction complicates the development of new drugs owing to altered efficacy of concomitant treatments, reduction in…”
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