Article
Pharmacology & Pharmacy
Ramzi Shawahna, Ahed Zyoud, Aseel Haj-Yahia, Raheek Taya
Summary: This study assessed the solubility of celecoxib in age-appropriate gastrointestinal media and identified potential age-related variability in the performance of oral formulations containing celecoxib in pediatric populations. The findings suggest that the criteria used for adults may not directly apply to pediatric subpopulations.
Article
Pharmacology & Pharmacy
Dong Ye, Alvaro Lopez Marmol, Verena Lenz, Patricia Muschong, Anita Wilhelm-Alkubaisi, Manuel Weinheimer, Mirko Koziolek, Kerstin A. Sauer, Loic Laplanche, Mario Mezler
Summary: The mucin-protected Caco-2 assay combined with biorelevant media improves the mechanistic understanding of drug permeation and addresses complex biopharmaceutical questions, such as food effects on oral drug absorption.
Article
Pharmacology & Pharmacy
Siddharth S. Kesharwani, Fady Ibrahim
Summary: This study aimed to investigate the precipitation behavior of cinnarizine in FaSSIF using biorelevant in vitro tools and GastroPlus(R) modeling, to identify the factors contributing to the observed variability in clinical plasma profiles. The study found that cinnarizine demonstrated variable precipitation rates under different bile salt concentrations, which could impact the concentration of the drug available for absorption. The results also showed that a precipitation-integrated modeling approach accurately predicted the mean plasma profiles from the clinical studies.
Article
Pharmacology & Pharmacy
Qamar Abuhassan, Ibrahim Khadra, Kate Pyper, Patrick Augustijns, Joachim Brouwers, Gavin W. Halbert
Summary: The solubility of drugs in intestinal fluid is important for the absorption of solid oral dosage forms. This study used a multidimensional approach to analyze fasted intestinal fluids and derived nine bioequivalent fasting intestinal media. These media were used to examine the solubility of twenty-one drugs and provided consistent solubility behavior in most cases, with control factors including media pH and total amphiphile concentration (TAC).
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2022)
Article
Pharmacology & Pharmacy
Bayan E. Ainousah, Ibrahim Khadra, Gavin W. Halbert
Summary: Solubility is a critical parameter for drug absorption after oral administration. This study investigated the impact of excipients on the solubility of fenofibrate in simulated intestinal media. The results showed that the impact of excipients on solubility is a complex interplay of media composition, physicochemical properties, and concentration.
Article
Cell Biology
Dipak Kumar Sahoo, Marilyn N. Martinez, Kimberly Dao, Vojtech Gabriel, Christopher Zdyrski, Albert E. Jergens, Todd Atherly, Chelsea A. Iennarella-Servantez, Laura E. Burns, Dwayne Schrunk, Donna A. Volpe, Karin Allenspach, Jonathan P. Mochel
Summary: To study the effects of drug-intestinal barrier interactions on therapeutic failure or toxicity, new methods are needed to evaluate drug-gut interactions in veterinary medicine. Three-dimensional (3D) organoids can provide a cost-effective system to address these difficulties without invasive in vivo assays. In this study, we demonstrate the growth and differentiation of canine-colonoid-derived intestinal epithelial cells in a 2D monolayer, and evaluate the permeability of passive beta-blockers in this canine-derived 2D model. The results show promising potential for species-specific assessments of drug permeability.
Article
Pharmacology & Pharmacy
Norraseth Kaeokhamloed, Emillie Roger, Jerome Bejaud, Nolwenn Lautram, Florence Manero, Rodolphe Perrot, Chadi Abbara, Marie Briet, Samuel Legeay
Summary: The study developed a coculture model of Caco-2 epithelium and HMEC-1 for evaluating the intestinal absorption of drugs and nanoparticles. Surface modification was found to alter the absorption mechanism of lipid nanocapsules.
Article
Chemistry, Applied
Yu-Ju Lin, Zijin Qin, Chad M. Paton, Douglas M. Fox, Fanbin Kong
Summary: The study found that CNC may not penetrate the small intestinal lining and could be used as a functional supplement.
CARBOHYDRATE POLYMERS
(2021)
Article
Pharmacology & Pharmacy
Yusuke Kamiya, Asuka Omura, Riku Hayasaka, Rie Saito, Izumi Sano, Kentaro Handa, Junya Ohori, Masato Kitajima, Fumiaki Shono, Kimito Funatsu, Hiroshi Yamazaki
Summary: The study found that the observed influx and efflux logP(app) values determined by in vitro experiments significantly correlated with molecular weights and the octanol-water distribution coefficients at different pH levels. Prediction accuracy was enhanced by applying a light gradient boosting machine learning system (LightGBM).
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ana Sofia Almeida, Barbara Silva, Fernando Remiao, Carla Fernandes
Summary: This study presents the first determination of the permeability of MDPV across an intestinal epithelial cell monolayer. The enantiomers of MDPV were found to have high permeability across the Caco-2 monolayer. Enantioselectivity and efflux through a facilitated diffusion mechanism were also observed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Mai Itagaki, Noriyasu Kamei, Mariko Takeda-Morishita
Summary: This study evaluated human induced pluripotent stem cell-derived small intestinal epithelial cells (hiPSC-SIECs) as a new model for predicting intestinal drug absorption. The results showed that hiPSC-SIECs are more suitable for predicting the absorption of peptide drugs compared to Caco-2 cells, require divalent cations for barrier integrity, and have different responses to absorption enhancers than Caco-2 cells.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Miao Zhang, Bin Wu, Shudong Zhang, Lin Wang, Qin Hu, Dongyang Liu, Xijing Chen
Summary: Solid drugs may undergo precipitation and redissolution after emptying from the stomach to the small intestine, affecting the absorption characteristics of compounds. Precipitates have advantageous properties compared to active pharmaceutical ingredients (API), but their permeability may differ. Therefore, understanding the physicochemical properties of precipitates and API is crucial for improving absorption prediction performance.
Article
Pharmacology & Pharmacy
Maria Ines Silva, Ibrahim Khadra, Kate Pyper, Gavin W. Halbert
Summary: This study investigates the solubility of 24 drugs in different simulated fed intestinal media and finds that the solubility of acidic drugs is mainly controlled by the pH of the media, while the solubility of weakly acidic, basic, and neutral drugs is controlled by both pH and total amphiphile concentration. By using two bioequivalent fed intestinal media, the maximum and minimum solubility values of most drugs can be determined in vitro.
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2023)
Article
Chemistry, Analytical
Miguel Xavier, Patricia M. Rodrigues, Mafalda D. D. Neto, Maria I. I. Guedes, Victor Calero, Lorenzo Pastrana, Catarina Goncalves
Summary: This article introduces a modular microfluidic-based platform for simulating the human gastrointestinal tract in vitro, which is essential for studying the bioavailability, intestinal absorption, and bioaccessibility of food ingredients or drugs. The platform utilizes digestion-chips and gut-chips to mimic the human gastrointestinal system, and has been validated to be effective and promising for pharmacokinetic studies.
Article
Multidisciplinary Sciences
Maria Hahn, Viktoria Lindemann, Matthias Behrens, Dennis Mulac, Klaus Langer, Melanie Esselen, Hans-Ulrich Humpf
Summary: This study investigated the transfer and transport of Hordenine in the human body and found that it can rapidly penetrate the intestinal epithelium and the blood-brain barrier, potentially accumulating in the brain. Additionally, Hordenine in the bloodstream may undergo absorption and metabolism in the intestines, reducing its bioavailability.
Review
Oncology
C. Markopoulos, D. M. Hyams, H. L. Gomez, M. Harries, S. Nakamura, T. Traina, A. Katz
Article
Pharmacology & Pharmacy
Marina Statelova, Rene Holm, Nikoletta Fotaki, Christos Reppas, Maria Vertzoni
Article
Pharmacology & Pharmacy
Alexandra-Roxana Ilie, Brendan T. Griffin, Martin Brandl, Annette Bauer-Brandl, Ann-Christin Jacobsen, Maria Vertzoni, Martin Kuentz, Ruzica Kolakovic, Rene Holm
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2020)
Article
Chemistry, Medicinal
Maria Vertzoni, Sarah Sulaiman, Konstantinos Goumas, Elisabeth Kersten, Johanna Anlahr, Uwe Muenster, Christos Reppas
Summary: This study characterized the contents of the distal ileum and proximal colon in older individuals compared to young adults, revealing differences in pH, buffer capacity, fatty acid concentrations, and osmolality. These findings suggest that the performance of certain modified release products may vary between older adults and the typical age group used in drug product studies.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Review
Pharmacology & Pharmacy
Patrick J. O'Dwyer, Karl J. Box, Jennifer Dressman, Brendan T. Griffin, Laura J. Henze, Chara Litou, Christina Pentafragka, Marina Statelova, Maria Vertzoni, Christos Reppas
Summary: The PEARRL project made significant contributions by optimizing existing biopharmaceutics tools and developing new tools for evaluating oral drug products both during drug development and at the regulatory level. The project successfully simplified the composition of biorelevant media for simulating fed state conditions, proposed strategies for incorporating in vitro data into PBPK modelling, and developed novel biopharmaceutics tools for better understanding drug effects. Through networking opportunities and research collaborations, the project achieved substantial progress in advancing biopharmaceutics tools for drug formulation screening and regulatory support.
JOURNAL OF PHARMACY AND PHARMACOLOGY
(2021)
Review
Pharmacology & Pharmacy
Zahari Vinarov, Bertil Abrahamsson, Per Artursson, Hannah Batchelor, Philippe Berben, Andreas Bernkop-Schnurch, James Butler, Jens Ceulemans, Nigel Davies, Didier Dupont, Goril Eide Flaten, Nikoletta Fotaki, Brendan T. Griffin, Vincent Jannin, Janneke Keemink, Filippos Kesisoglou, Mirko Koziolek, Martin Kuentz, Alan Mackie, Antonio J. Melendez-Martinez, Mark McAllister, Anette Mullertz, Caitriona M. O'Driscoll, Neil Parrott, Jadwiga Paszkowska, Petr Pavek, Christopher J. H. Porter, Christos Reppas, Cordula Stillhart, Kiyohiko Sugano, Elena Toader, Katerina Valentova, Maria Vertzoni, Saskia N. De Wildt, Clive G. Wilson, Patrick Augustijns
Summary: The review article discusses the challenges and gaps in understanding oral drug absorption processes, focusing on specific patient populations, regional differences in the gastrointestinal tract, advanced formulations, and food-drug interactions. Controversies and gaps in current knowledge are identified to pave the way for future research in the field of oral drug absorption.
ADVANCED DRUG DELIVERY REVIEWS
(2021)
Review
Pharmacology & Pharmacy
Zahari Vinarov, Mohammad Abdallah, Jose A. G. Agundez, Karel Allegaert, Abdul W. Basit, Marlies Braeckmans, Jens Ceulemans, Maura Corsetti, Brendan T. Griffin, Michael Grimm, Daniel Keszthelyi, Mirko Koziolek, Christine M. Madla, Christophe Matthys, Laura E. McCoubrey, Amitava Mitra, Christos Reppas, Jef Stappaerts, Nele Steenackers, Natalie L. Trevaskis, Tim Vanuytsel, Maria Vertzoni, Werner Weitschies, Clive Wilson, Patrick Augustijns
Summary: Variability in the absorption of oral drugs can be attributed to differences in physiology, special populations, drug properties, and food-drug interactions. Pharmaceutical formulation approaches have been shown to reduce variability in oral drug exposure, but there are still gaps in understanding the impact of colonic factors, sex differences, and gut-related diseases on drug absorption variability.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Patrick J. O'Dwyer, Karl J. Box, Georgios Imanidis, Maria Vertzoni, Christos Reppas
Summary: This study evaluated various in vitro methods for assessing the intraluminal performance of low solubility drugs in the fasted state, finding that the choice of methodology depends on the characteristics of the drug substance. Specifically, for salts of acidic drugs like diclofenac potassium, availability and ease of operation of the apparatus are key factors, while for weakly alkaline substances like ritonavir, dynamic dissolution process simulation and specific information requirements are crucial in method selection. Early in drug development, the use of small-scale systems may be necessary due to limited drug substance quantities available.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Pharmacology & Pharmacy
M. Vertzoni, J. Alsenz, P. Augustijns, A. Bauer-Brandl, C. A. S. Bergstrom, J. Brouwers, A. Mullerz, G. Perlovich, C. Saal, K. Sugano, C. Reppas
Summary: The COST UNGAP aims to standardize methods for studying oral drug absorption, emphasizing the importance of solubility data for drug development and regulation, and addressing factors that affect data quality.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Editorial Material
Chemistry, Medicinal
Bertil Abrahamsson, James Butler, Rodrigo Cristofoletti, Edmund Kostewicz, Christoph Saal, Christos Reppas
JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Chemistry, Medicinal
Christina Pentafragka, Irena Tomaszewska, Susann Bellmann, Mans Minekus, Ronald Schilderink, Maria Vertzoni, Mark McAllister, Christos Reppas
Summary: In this study, the environment in TIM-1 luminal compartments was evaluated and compared with data from healthy adults. The results showed that the gastric and duodenal compartments of TIM-1 accurately reflected the luminal conditions in adults, but there was an overestimation of bile acid concentrations. Adjustments in gastric emptying/acid secretion rates and bile acids identities are expected to improve the relevance of luminal conditions in TIM-1 compartments with those in adults.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Pathology
Keying Xu, Jane Bayani, Elizabeth Mallon, Gregory R. Pond, Tammy Piper, Annette Hasenburg, Christos J. Markopoulos, Luc Dirix, Caroline M. Seynaeve, Cornelis J. H. van de Velde, Daniel W. Rea, John M. S. Bartlett
Summary: Based on quantitative molecular analysis of breast cancers using RNA expression, this study found that the dynamic range of HER2 expression in HER2-low expressing breast cancers exceeds the detection range of current immunohistochemistry methods. It suggests that defining HER2-low cancers based on RNA abundance may better serve treatment decision needs. However, further evaluation through prospective clinical trials is needed to validate the efficacy of RNA abundance in identifying HER2-low cancers and predicting treatment response.
JOURNAL OF MOLECULAR DIAGNOSTICS
(2022)
Review
Psychology, Clinical
Karveli Spyridoula, Galanis Petros, Mitropoulou Eirini Marina, Karademas Evangelos, Markopoulos Christos
Summary: This review study found that attachment anxiety or avoidance can affect the quality of life and distress of early-stage breast cancer patients. Insecure attachment is related to poorer quality of life and higher levels of distress, while avoidant attachment is more frequent and associated with more negative outcomes. Healthcare providers should investigate modifiable personality traits during the initial diagnosis period to identify patients who are more vulnerable to mental health problems, provide personalized care, and reduce emotional burden.
JOURNAL OF CLINICAL PSYCHOLOGY IN MEDICAL SETTINGS
(2023)
Article
Pharmacology & Pharmacy
Lea Gnatzy, George Ismailos, Maria Vertzoni, Christos Reppas
Summary: Intestinal dysbiosis refers to changes in the intestinal microbiota that are associated with the development and worsening of diseases in humans. This review briefly presents the clinical effects of drug-induced intestinal dysbiosis and critically reviews methodologies for managing it based on clinical data. A pharmacokinetically-based approach is proposed for mitigating the impact of antimicrobial therapy on intestinal dysbiosis, but further optimization and confirmation of effectiveness to the general population are needed.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Meeting Abstract
Oncology
Andreas Karakatsanis, Theodoros Foukakis, Per Karlsson, Eleftherios Mamounas, Anees Chagpar, John Boyages, Isabel Rubio, Bjorn Naume, Davide Mauri, Elsken van der Wall, Chirag Shah, Ava Kwong, Priscilla McAuliffe, Oreste Gentilini, Michail Ignatiadis, Ellen Schlichting, Janez Zgajnar, Francesco Meani, Marios Konstantinos Tasoulis, Pat Whitworth, Walter Weber, Petros Charalampoudis, Bahadir Gulluoglu, Lida Pistioli, Tove Filtenborg Tvedskov, Marjut Leidenius, Bruce Mann, Arjen Witkamp, Lynda Wyld, Rosa di Micco, Christos Markopoulos, Antonios Valachis, Fredrik Warnberg
ANNALS OF SURGICAL ONCOLOGY
(2020)