Results 21 to 30 of about 5,951 (176)

Repurposing Drugs for Malaria through a Human Dose Prediction: A Case Study with Berzosertib

Clinical Pharmacology &Therapeutics, EarlyView.
Repurposing drugs whose clinical safety has been established offers a valuable approach to reduce the cost and time associated with the development of new drugs for malaria. Here, we investigate the potential to repurpose the anticancer kinase inhibitor berzosertib for the treatment of malaria, by assessing whether a predicted efficacious human dose ...
Devasha Redhi, Mwila Mulubwa, Mmakwena M. Mmonwa, Mathew Njoroge, Liezl Krugmann, Kelly Chibale   +5 more
wiley   +1 more source

AI‐Enabled Precision Dosing in Pediatrics: Enhancing Model‐Informed Decision Making

Clinical Pharmacology &Therapeutics, EarlyView.
Ensuring safe and effective pharmacotherapy for children remains a central challenge in clinical pharmacology, yet rapid advances in AI have not translated into clinical practice. This Perspective highlights how AI‐enabled approaches can enhance model‐informed decision making for precision dosing.
Kei Irie, Tomoyuki Mizuno
wiley   +1 more source

Characterization of Lysosomal Hydrolases and Transporters and Their Age‐Dependent Variability: Relevance to Drug Metabolism and Transport of Small Molecule and Biologic Drugs

Clinical Pharmacology &Therapeutics, EarlyView.
Lysosomes play a key role in the accumulation, catabolism, and transport of endogenous and exogenous metabolites and proteins and are involved in drug metabolism and prodrug activation. However, the protein abundance and interindividual variability of lysosomal drug‐metabolizing enzymes and transporters (DMETs) remain underexplored.
Darshak Gadara, Dilip Kumar Singh, Sandhya Subash, Guihua Yue, Deepak Ahire, Chris Bohl, Maciej Czerwinski, Stephanie Helmstetter, Scott Heyward, Robert S. Jones, Cyrus Khojasteh, Ryota Kikuchi, Priyanka Kulkarni, Bin Ma, Bernard Murray, Chris Seib, Bill Smith, David M. Stresser, Mitchell E. Taub, Ting Wang, Bhagwat Prasad   +20 more
wiley   +1 more source

Virtual Twin Approach Using Physiologically Based Pharmacokinetic Modeling to Support Precision Dosing of Valproic Acid in Geriatric Patients

Clinical Pharmacology &Therapeutics, EarlyView.
Personalized dosing is particularly important for drugs with narrow therapeutic indices in geriatric patients, who exhibit substantial physiological variability and limited pharmacokinetic (PK) evidence to guide individualized dose selection. Valproic acid (VPA) is an effective treatment option for bipolar disorder in older adults, yet dosing largely ...
Yoo Jin Jang, Dong‐Gyu Heo, Eunjin Hong   +2 more
wiley   +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

Toward the harmonization of bioequivalence guidelines in Europe: Commentary on the state of the art and future priorities under ICH M13A for immediate‐release oral forms

British Journal of Clinical Pharmacology, EarlyView.
Domenico Nocera, Giusi Forastiero, Andrea Logreco, Alessia Proietti, Antonio Galluccio, Carlotta Lunghi, Elisabetta Poluzzi, Fabrizio De Ponti   +7 more
wiley   +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

Model‐Informed Evaluation of Hydroxyurea Exposure During Lactation

Clinical Pharmacology &Therapeutics, EarlyView.
Hydroxyurea is a cornerstone therapy for sickle cell anemia; however, evidence guiding its use during lactation remains limited. This study aimed to develop a population pharmacokinetic (PK) model to characterize hydroxyurea disposition in maternal plasma and breast milk, and to quantify infant exposure under clinically relevant breastfeeding scenarios.
Anhar Hosawi, Kei Irie, Min Dong, Julie Ware, Russell Ware, Tomoyuki Mizuno   +5 more
wiley   +1 more source

Integrated assessment of rifampicin‐mediated induction of transporters and drug‐metabolizing enzymes in a long‐term human liver tissue chip system

Clinical Pharmacology &Therapeutics, EarlyView.
Rifampicin is a prototypical clinical inducer used in drug–drug interaction (DDI) studies. However, the clinical relevance and predictability of rifampicin‐mediated hepatic transporter induction remain poorly defined. Conventional hepatocyte culture models fail to capture clinically relevant regulation of transporters and drug‐metabolizing enzymes ...
Mattie E. Hartauer, Raeanne M. Lanphier, Shivam Ohri, Jessica Snyder, Jacqueline B. Tiley, John K. Fallon, Henry Ho, Murat Cirit, Shiny Amala Priya Rajan, Kim L. R. Brouwer   +9 more
wiley   +1 more source

The gut microbiome and drug‐resistant epilepsy: Microbiome–antiseizure medication interactions and implications for pharmacoresistance

Epilepsia Open, EarlyView.
Abstract Drug‐resistant epilepsy (DRE) affects approximately one‐third of patients with epilepsy and represents a major unmet clinical need. While traditional hypotheses of pharmacoresistance have focused on alterations in drug targets, efflux transporter overexpression, and intrinsic disease severity, the gut microbiome has recently emerged as a ...
Khaled Zammar, Majd A. AbuAlrob, Musab Ali, Simona Lattanzi, Boulenouar Mesraoua   +4 more
wiley   +1 more source