Results 101 to 110 of about 9,895 (222)

A Physiologically-Based Pharmacokinetic (PBPK) Model Network for the Prediction of CYP1A2 and CYP2C19 Drug–Drug–Gene Interactions with Fluvoxamine, Omeprazole, S-mephenytoin, Moclobemide, Tizanidine, Mexiletine, Ethinylestradiol, and Caffeine

Pharmaceutics, 2020
Physiologically-based pharmacokinetic (PBPK) modeling is a well-recognized method for quantitatively predicting the effect of intrinsic/extrinsic factors on drug exposure.
Tobias Kanacher, Andreas Lindauer, Enrica Mezzalana, Ingrid Michon, Celine Veau, Jose David Gómez Mantilla, Valerie Nock, Angèle Fleury   +7 more
doaj   +1 more source

Quantitative Systems Toxicology Model Predicts Obeticholic Acid‐Associated Liver Injury in Metabolic Dysfunction‐Associated Steatotic Liver Disease

Clinical Pharmacology &Therapeutics, EarlyView.
Obeticholic acid (OCA), a synthetic analog of chenodeoxycholic acid, was approved in 2016 for the treatment of primary biliary cholangitis. Early clinical trials revealed elevated liver biomarkers in healthy subjects receiving supratherapeutic OCA doses (100–250 mg).
Abigail K. Mayo, James J. Beaudoin, Jeffrey L. Woodhead, Paul B. Watkins, Kim L. R. Brouwer   +4 more
wiley   +1 more source

Physiologically‐Based Pharmacokinetic Modeling to Support Pediatric Clinical Development: An IQ Working Group Perspective on the Current Status and Challenges

CPT: Pharmacometrics & Systems Pharmacology
Pediatric extrapolation strategies issued by health authorities have streamlined pediatric drug development and reduced the unnecessary burden of conducting pediatric clinical studies. In line with these strategies, physiologically based pharmacokinetic (
James W. T. Yates, Michael Zientek, Kunal S. Taskar, Wen Lin, Tycho Heimbach, Stefan Willmann, Jessica Rehmel, Neil Parrott, Michael Hanley, Justine Badee, Yuan Chen, Susan Cole, Loeckie De Zwart, Sebastian Haertter, Rongrong Jiang, Masakatsu Kotsuma, Guiqing Liang, Yu‐Wei Lin, Jing Liu, Ying Ou, Juliane Rascher, Naveed A. Shaik, Jan Wahlstrom, Xiaofeng Wang, Guangqing Xiao, Ka Lai Yee, S. Y. Amy Cheung   +26 more
doaj   +1 more source

Utilizing in vitro transporter data in IVIVE-PBPK: an overview [PDF]

, 2017
In vitro-in vivo extrapolation (IVIVE) integrated in physiologically-based pharmacokinetic (PBPK) models have been increasingly used during drug discovery and development processes to predict human pharmacokinetic (PK) parameters.
Mallick, Pankajini, Pankajini Mallick
core   +1 more source

Application of Virtual Twin PBPK Models in Individuals with Obesity via CYP3A4 Phenotyping Using Endogenous Biomarker Data

Clinical Pharmacology &Therapeutics, EarlyView.
Plasma 4β‐hydroxycholesterol (4β‐OHC) normalized for the levels of its parent cholesterol (4β‐OHC/C) is an endogenous biomarker for hepatic CYP3A4. This study evaluated CYP3A4 activity longitudinally in individuals while their obesity status was changing. 4β‐OHC/C was measured pre‐surgery (n = 54) and 2 years after Roux‐en‐Y gastric bypass (n = 30) and
Nihan Izat, Haribhau Kangne, Rasmus Jansson‐Löfmark, Jens K. Hertel, Amin Rostami‐Hodjegan, Ida Robertsen, Aleksandra Galetin   +6 more
wiley   +1 more source

Physiologically Based Pharmacokinetic (PBPK) Modeling to Predict CYP3A-Mediated Drug Interaction between Saxagliptin and Nicardipine: Bridging Rat-to-Human Extrapolation

Pharmaceutics
The aim of this study was to predict the cytochrome P450 3A (CYP3A)-mediated drug–drug interactions (DDIs) between saxagliptin and nicardipine using a physiologically based pharmacokinetic (PBPK) model.
Jeong-Min Lee, Jin-Ha Yoon, Han-Joo Maeng, Yu Chul Kim   +3 more
doaj   +1 more source

Clinical Characterization of Enzyme and Transporter Precipitants to Evaluate Drug–Drug Interactions for Orforglipron, a Small Molecule Glucagon‐Like Peptide‐1 Receptor Agonist

Clinical Pharmacology &Therapeutics, EarlyView.
Orforglipron is an orally administered, small‐molecule glucagon‐like peptide‐1 receptor agonist in clinical development for the treatment of type 2 diabetes and obesity. Orforglipron is a substrate of CYP3A4, organic anion transporting polypeptides (OATPs) 1B/1B3, and P‐glycoprotein (P‐gp); however, precipitants commonly used to define these mechanisms
Bridget L. Morse, David E. Coutant, Xiaosu Ma, Sohini Raha, Keerthan Aithal, Clare Nicoll, Luc R. A. Rougée, Shobha Bhattachar   +7 more
wiley   +1 more source

From Executor to Orchestrator: The Pharmacology Scientist in the Age of Agentic AI

Clinical Pharmacology &Therapeutics, EarlyView.
Drug development productivity has not improved despite five decades of computational advancement, with the probability that a compound entering Phase I achieving regulatory approval remaining near 10%. Each automation wave increased throughput while leaving the interpretive bottleneck intact; scientists continued to formulate questions, evaluate ...
Michael McCoy, Matthew McCoy
wiley   +1 more source

Codeine and Metabolite Concentrations in the Breastfed Neonate

Pediatric Anesthesia, EarlyView.
ABSTRACT Analgesic effect from codeine is from its metabolite, morphine. Morphine is formed by the O‐demethylation of codeine and that enzyme is controlled by the cytochrome P450 2D6. More than 60 alleles in the CYP2D6 gene have been identified. This spectrum of polymorphism can be categorized into four groups: poor (PM), intermediate (IM), normal (NM),
Brian J. Anderson, Jacqueline A. Hannam
wiley   +1 more source

Plasma Lidocaine Concentrations During Intravenous Lidocaine Infusion Therapy in the Pediatric Population—A Scoping Review

Pediatric Anesthesia, EarlyView.
ABSTRACT Background Intravenous lidocaine therapy (IVLT) is often used in perioperative multimodal analgesia due to its analgesic, anti‐hyperalgesic, and anti‐inflammatory effects. In adults, IVLT doses of 1–2 mg/kg/h produce plasma concentrations of 1–2 μg/mL, within the presumed therapeutic range of 1–5 μg/mL.
McKenna Postles, Amanda Barton, Nicholas West, Gillian Lauder   +3 more
wiley   +1 more source