Article
Clinical Neurology
Priska Kaufmann, Marion Ort, Georg Golor, Ruediger Kornberger, Jasper Dingemanse
Summary: Selective orexin-1 receptor antagonists like ACT-539313 show activity on the CNS and a potential decrease in anxiety/panic symptoms. Clinical studies demonstrate good safety and tolerability of multiple doses of ACT-539313, supporting further investigations into its pharmacological properties.
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
(2021)
Article
Microbiology
Sinenhlanhla Mtshali, Byron A. Jacobs
Summary: Physiologically based pharmacokinetic models have gained popularity in drug development and regulatory science. This study validates the model's effectiveness in predicting drug-drug interaction and the pharmacokinetics of antiretroviral and anti-TB drugs through mathematical solving and sensitivity analysis.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Rehabilitation
Gerasimos Bastas, Jonathan Dallas, Patricia Blair Miller, Nicole Kloosterman, Ion Yannopoulos
Summary: Most major limb amputation cases involve polypharmacy preoperatively and increased medication use or maintenance postoperatively. Drug-drug interaction warnings also increase, indicating the need for further research and clinical attention.
AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION
(2021)
Article
Medicine, Research & Experimental
Jasper Dingemanse, Pascal Charef, Jed Black, Chris Gouws
Summary: This study found that a 4-week once daily administration of 200 mg almorexant did not have any treatment effects on tear film break-up time, spermatogenesis, hormone levels, or pancreatic elastase in stool in healthy male subjects. The drug was well tolerated and did not show any adverse effects on the variables assessed. Preclinical findings related to ophthalmology and testicular function did not translate to humans in this clinical study, indicating the need for larger clinical trials.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Engineering, Chemical
Muzaffar Iqbal, Mohammad Raish, Ajaz Ahmad, Essam A. Ali, Yousef A. Bin Jardan, Mushtaq A. Ansari, Mudassar Shahid, Abdul Ahad, Khalid M. Alkharfy, Fahad I. Al-Jenoobi
Summary: The study found that when Ibrutinib interacts with Sinapic acid, it may influence the pharmacokinetics of Ibrutinib and result in increased bioavailability. This may be due to the inhibition of IBR metabolism in the liver and intestines by SA.
Article
Pharmacology & Pharmacy
Boyu Fang, Shasha Jin, Wandi Du, Weimin Cai
Summary: A study has found that co-administration of vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) and anticoagulants increases the risk of bleeding. This raises concerns about the potential pharmacokinetic and pharmacodynamic interaction between TKIs and warfarin, which is used by tumor patients for DVT prevention.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Sukyong Yoon, Min Soo Park, Byung Hak Jin, Hyobin Shin, Jaejin Na, Wan Huh, Choon Ok Kim
Summary: This study evaluated the pharmacokinetic and pharmacodynamic interactions of DWP16001 and phentermine, and found that the combination therapy was similar to monotherapy in terms of PK and PD. The combination therapy group may contribute to weight loss, and participants tolerated the treatment well.
EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY
(2023)
Review
Pharmacology & Pharmacy
Nicola Ferri, Elisa Colombo, Marco Tenconi, Ludovico Baldessin, Alberto Corsini
Summary: Direct oral anticoagulants (DOACs) are frequently prescribed to prevent ischemic stroke in non-valvular atrial fibrillation (NVAF) patients and treat venous thromboembolism (VTE). They have a favorable risk-benefit profile compared to warfarin but may increase the risk of gastrointestinal bleeding. Polypharmacy and comorbidity in elderly patients can lead to drug-drug interactions (DDIs) with DOACs. This review summarizes potential DDIs and discusses strategies to reduce their occurrence.
Article
Medicine, Research & Experimental
Lamya S. Alnaim, Hind M. Almalki, Afrah M. Almutairi, Heba J. Salamah
Summary: The prevalence of drug-drug interactions (DDIs) in cancer patients is high, especially due to the multiple medications they receive. Factors such as the number of drugs, type of treatment, and length of stay in hospital contribute to the occurrence of DDIs.
Article
Multidisciplinary Sciences
Adam D. Collier, Nushrat Yasmin, Nailya Khalizova, Samantha Campbell, Amanda Onoichenco, Milisia Fam, Avi S. Albeg, Sarah F. Leibowitz
Summary: Research in zebrafish has shown that embryonic exposure to ethanol can increase the number of Hcrt neurons and have long-lasting effects on behavior. Sexually dimorphic effects were observed in adults, with females consuming more ethanol and exhibiting more freezing behavior while males showed increased aggression.
SCIENTIFIC REPORTS
(2021)
Article
Infectious Diseases
Pierre Chauvelot, Celine Dupieux-Chabert, Lelia Abad, Aubin Souche, Tristan Ferry, Jerome Josse, Frederic Laurent, Florent Valour
Summary: The study demonstrated that dalbavancin has the ability to effectively eradicate intraosteoblastic reservoir of Staphylococcus aureus in bone and joint infections. It showed significant reduction in bacterial inoculum at both low concentration and standard therapeutic doses, with similar efficacy to vancomycin but less efficient than rifampicin. Dalbavancin was found to be the only molecule significantly active at a low concentration.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2021)
Article
Endocrinology & Metabolism
Ki Young Huh, Jun Gi Hwang, Wonjung Shin, Seungjae Baek, JaeDuk Choi, Nora Lee, Young Min Cho, Howard Lee
Summary: HM15136, a novel long-acting glucagon analogue, was shown to be safe and well tolerated in doses ranging from 10-120 μg/kg in a randomized, double-blind, placebo-controlled study. It increased blood glucose levels and suppressed the secretion of endogenous glucagon.
DIABETES OBESITY & METABOLISM
(2022)
Article
Cell Biology
Nushrat Yasmin, Adam D. D. Collier, Abdul R. R. Abdulai, Olga Karatayev, Boyi Yu, Milisia Fam, Sarah F. F. Leibowitz
Summary: Studies in zebrafish and rats have shown that low-moderate concentrations of ethanol exposure during embryonic development can stimulate hypothalamic neurons that promote alcohol consumption. This effect may involve the chemokine Cxcl12 and its receptor Cxcr4. Recent studies in zebrafish have further demonstrated that ethanol exposure has specific effects on certain subpopulations of these neurons, increasing their number in certain areas and causing them to become ectopically expressed in a different region. Genetic manipulation experiments revealed that Cxcl12a plays a crucial role in mediating these effects of ethanol on the development of the neuronal system.
Review
Pharmacology & Pharmacy
Li Zhou, Micaela B. Reddy, Rajendar K. Mittapalli, Jing Yang, Donghua Yin
Summary: Combination therapies are commonly evaluated in the clinical development of oncology investigational agents, and the design needs to consider factors such as drug interactions and benefit/risk to study participants. This report proposes application scenarios for different trial designs and emphasizes the importance of generating robust exposure-response data for optimal dose selection.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Pharmacology & Pharmacy
Ana Alarcia-Lacalle, Helena Barrasa, Javier Maynar, Andres Canut-Blasco, Carmen Gomez-Gonzalez, Maria Angeles Solinis, Arantxazu Isla, Alicia Rodriguez-Gascon
Summary: This study developed a rapid, simple and reproducible HPLC-UV method for quantifying ceftaroline in plasma samples, which was accurate and stable, successfully applied in two critically ill patients.
Article
Pharmacology & Pharmacy
Margaux Boehler, Pierre-Eric Juif, Matthias Hoch, Jasper Dingemanse
EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS
(2017)
Article
Pharmacology & Pharmacy
Pierre-Eric Juif, Matthias Hoch, Andrea Vaclavkova, Andreas Krause, Jim Bush, Jasper Dingemanse
JOURNAL OF CLINICAL PHARMACOLOGY
(2017)
Article
Oncology
Erika P. Hamilton, Manish R. Patel, Anne C. Armstrong, Richard D. Baird, Komal Jhaveri, Matthias Hoch, Teresa Klinowska, Justin P. O. Lindemann, Shethah R. Morgan, Gaia Schiavon, Hazel M. Weir, Seock-Ah Im
CLINICAL CANCER RESEARCH
(2018)
Article
Pharmacology & Pharmacy
Tashinga E. Bapiro, Andy Sykes, Scott Martin, Michael Davies, James W. T. Yates, Matthias Hoch, Helen E. Rollison, Barry Jones
DRUG METABOLISM AND DISPOSITION
(2018)
Review
Chemistry, Medicinal
Domagoj Segregur, Talia Flanagan, James Mann, Andrea Moir, Eva M. Karlsson, Matthias Hoch, David Carlile, Sakina Sayah-Jeanne, Jennifer Dressman
JOURNAL OF PHARMACEUTICAL SCIENCES
(2019)
Article
Pharmacology & Pharmacy
Matthias Hoch, Masahiko Sato, Julia Zack, Michelle Quinlan, Tirtha Sengupta, Alex Allepuz, Paola Aimone, Florence Hourcade-Potelleret
Summary: These findings indicate that renal or hepatic impairment has no clinically meaningful effect on the exposure or safety profile of asciminib, supporting its use in patients with varying degrees of renal or hepatic dysfunction.
JOURNAL OF CLINICAL PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Matthias Hoch, Julia Zack, Michelle Quinlan, Felix Huth, Sofia Forte, Stephanie Dodd, Paola Aimone, Florence Hourcade-Potelleret
Summary: The study showed that coadministration of asciminib with imatinib and a low-fat meal resulted in a moderate increase in asciminib exposure compared with asciminib alone under the same food condition. However, food itself decreased asciminib exposure, suggesting that single-agent asciminib should be administered in the fasted state to prevent suboptimal exposures.
CLINICAL PHARMACOLOGY IN DRUG DEVELOPMENT
(2022)
Article
Medicine, Research & Experimental
Matthias Hoch, Tirtha Sengupta, Florence Hourcade-Potelleret
Summary: Asciminib, a new treatment option for chronic myeloid leukemia patients, specifically targets the ABL Myristoyl Pocket (STAMP). This study evaluated the inhibitory effects of Asciminib on cytochrome P450 enzymes. The results showed that Asciminib is a weak inhibitor of CYP3A and CYP2C9.
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2022)
Article
Medicine, Research & Experimental
Matthias Hoch, Felix Huth, Masahiko Sato, Tirtha Sengupta, Michelle Quinlan, Stephanie Dodd, Shruti Kapoor, Florence Hourcade-Potelleret
Summary: This report summarizes the results of two phase I studies in healthy subjects evaluating the pharmacokinetics of Asciminib. The study found that the exposure of Asciminib decreased or increased when administered concomitantly with certain drugs. However, these changes were not considered clinically significant. The report also emphasized caution when administering Asciminib with drugs containing cyclodextrin.
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2022)
Article
Pharmacology & Pharmacy
Ying Fei Li, Francois Pierre Combes, Matthias Hoch, Sebastien Lorenzo, Sherwin K. B. Sy, Yu-Yun Ho
Summary: A population pharmacokinetic model was developed to describe the PK properties of asciminib and assess the impact of key covariates on its exposure. The model supported the approved asciminib dose of 80 mg total daily dose as 40 mg twice daily, and also supported the use of 80 mg once daily as an alternative dose regimen to improve patient compliance.
CLINICAL PHARMACOKINETICS
(2022)
Article
Pharmacology & Pharmacy
Francois Pierre Combes, Ying Fei Li, Matthias Hoch, Sebastien Lorenzo, Yu-Yun Ho, Sherwin K. B. Sy
Summary: Asciminib has potent activity against the T315I mutation in chronic myeloid leukemia patients. A longitudinal pharmacokinetic/pharmacodynamic model was developed to characterize the exposure-efficacy relationship of Asciminib. The model demonstrated the appropriateness of different doses for patients with or without the T315I mutation.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Pharmacology & Pharmacy
Matthias Hoch, Lidiya Bebrevska, Namrata Singh, Florence Hourcade-Potelleret
Summary: Asciminib is a first-in-class BCR-ABL1 inhibitor used for the treatment of chronic myeloid leukemia. This study evaluated the bioavailability of asciminib in pediatric formulation (1-mg mini-tablets) compared with the reference adult tablet, and found that food affects the bioavailability of the mini-tablet formulation. The mini-tablets were found to be easy to ingest with good palatability.
CLINICAL PHARMACOLOGY IN DRUG DEVELOPMENT
(2023)
Article
Oncology
Michael J. Mauro, Timothy P. Hughes, Dong-Wook Kim, Delphine Rea, Jorge E. Cortes, Andreas Hochhaus, Koji Sasaki, Massimo Breccia, Moshe Talpaz, Oliver Ottmann, Hironobu Minami, Yeow Tee Goh, Daniel J. DeAngelo, Michael C. Heinrich, Valle Gomez-Garcia de Soria, Philipp le Coutre, Francois-Xavier Mahon, Jeroen J. W. M. Janssen, Michael Deininger, Naranie Shanmuganathan, Mark B. Geyer, Silvia Cacciatore, Fotis Polydoros, Nithya Agrawal, Matthias Hoch, Fabian Lang
Summary: Asciminib has been approved for patients with Philadelphia chromosome-positive chronic-phase chronic myeloid leukemia (CML-CP) who have received >= 2 prior tyrosine kinase inhibitors or have the T315I mutation. A phase 1 trial evaluated the safety and efficacy of asciminib monotherapy in 115 CML-CP patients without T315I. After a median exposure of approximately 4 years, most patients remained on asciminib and achieved significant molecular responses.
Article
Oncology
Aurelija Jucaite, Per Stenkrona, Zsolt Cselenyi, Serena De Vita, Nuria Buil-Bruna, Katarina Varnas, Alicia Savage, Andrea Varrone, Peter Johnstrom, Magnus Schou, Chris Davison, Andy Sykes, Venkatesh Pilla Reddy, Matthias Hoch, Ana Vazquez-Romero, Mohammad Mahdi Moein, Christer Halldin, Melinda S. Merchant, Martin Pass, Lars Farde
Summary: The study demonstrates that AZD1390 can cross the intact blood-brain barrier and supports its development for treating brain malignancies. PET microdosing shows potential in predicting and guiding dose range and schedule for subsequent clinical studies.
Article
Oncology
Costanza Paoletti, Gaia Schiavon, Emily M. Dolce, Elizabeth P. Darga, T. Hedley Carr, Joseph Geradts, Matthias Hoch, Teresa Klinowska, Justin Lindemann, Gayle Marshall, Shethah Morgan, Parul Patel, Vicky Rowlands, Nitharsan Sathiyayogan, Kimberly Aung, Erika Hamilton, Manish Patel, Anne Armstrong, Komal Jhaveri, Seock-Ah Im, Nadia Iqbal, Fouziah Butt, Caroline Dive, Elizabeth A. Harrington, J. Carl Barrett, Richard Baird, Daniel F. Hayes
CLINICAL CANCER RESEARCH
(2018)
Article
Clinical Neurology
Hannah Meijs, Helena Voetterl, Alexander T. Sack, Hanneke van Dijk, Bieke De Wilde, Jan Van Hecke, Peter Niemegeers, Evian Gordon, Jurjen J. Luykx, Martijn Arns
Summary: This study used a polygenic score (PGS) and electroencephalography (EEG) data analysis to identify potential predictors for treatment outcomes in major depressive disorder (MDD). The results suggest the existence of a stable EEG network related to antidepressant-response that has potential as a predictor for MDD treatment, particularly in the case of venlafaxine.
EUROPEAN NEUROPSYCHOPHARMACOLOGY
(2024)