Article
Microbiology
Brian D. VanScoy, Elizabeth A. Lakota, Haley Conde, Steven Fikes, Sujata M. Bhavnani, Philippa B. Elefante, Nicole E. Scangarella-Oman, Paul G. Ambrose
Summary: The study aimed to determine the efficacy of gepotidacin against E. coli and its relationship with pharmacokinetic-pharmacodynamic (PK-PD) indexes, as well as to characterize the relationship between gepotidacin exposure and E. coli resistance amplification. Results showed that the gepotidacin free-drug AUC/MIC ratio was closely associated with changes in bacterial burden, and different AUC/MIC values were able to suppress E. coli growth and resistance development.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(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
Oncology
Richard J. Sove, Babita K. Verma, Hanwen Wang, Won Jin Ho, Mark Yarchoan, Aleksander S. Popel
Summary: This study uses quantitative systems pharmacology (QSP) framework to conduct a virtual clinical trial for nivolumab and ipilimumab in HCC patients. The model incorporates detailed biological mechanisms of immune cell-cancer cell interactions and generates virtual patients for the trial. The predictions of the model are consistent with clinically observed outcomes, demonstrating the potential of QSP models in patient selection and trial design.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Pharmacology & Pharmacy
Kei Xian Tan, Michael K. Danquah, Jaison Jeevanandam, Ahmed Barhoum
Summary: Janus particles have emerged as a novel and smart material for improving pharmaceutical formulation, drug delivery, and therapeutics. They have two distinct compartments that can accommodate opposing pharmaceutical agents and allow for controlled drug release. This article discusses the development of Janus particles and their potential applications in diabetes treatment and antimicrobial therapy. It highlights the advances in synthesizing Janus particles from different materials using various approaches and evaluates their potential for improving conventional drug delivery systems.
Article
Immunology
John P. O'Donnell, Sujata M. Bhavnani
Summary: Sulbactam-durlobactam is a combination of beta-lactam and beta-lactamase inhibitor that is being developed for the treatment of Acinetobacter infections, including multidrug-resistant strains. Sulbactam has intrinsic antibacterial activity against Acinetobacter, but its effectiveness has been reduced by increasing beta-lactamase-mediated resistance. Durlobactam, a rationally designed beta-lactamase inhibitor, effectively restores susceptibility to resistant isolates when combined with sulbactam. This review discusses the pharmacokinetic/pharmacodynamic relationship of the combination in nonclinical infection models and aids in determining effective dose regimens for humans.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Oncology
Ivan N. Terterov, Vyacheslav A. Chubenko, Nikolay A. Knyazev, Vladimir V. Klimenko, Andrei A. Bogdanov, Vladimir M. Moiseyenko, Alexey A. Bogdanov
Summary: The study proposed a simple model that can describe both metronomic chemotherapy and maximum tolerated dose regimens, and validated its efficacy through experimental data.
CANCER CHEMOTHERAPY AND PHARMACOLOGY
(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)
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.
Review
Infectious Diseases
Cornelia B. Landersdorfer, Amanda Gwee, Roger L. Nation
Summary: Traditionally, ongoing i.v. antibiotic therapy has been believed to be superior to early i.v. to oral switch for severe infections. However, this belief may not be based on robust data and contemporary clinical studies. This review examines the rationale for an early switch and discusses barriers and perceptions related to this practice.
CLINICAL MICROBIOLOGY AND INFECTION
(2023)
Article
Hematology
Julie Kanter, R. Clark Brown, Cynthia Norris, Santosh M. Nair, Abdullah Kutlar, Deepa Manwani, Nirmish Shah, Chiaki Tanaka, Shankaranand Bodla, Gessami Sanchez-Olle, Urs Albers, Darla Liles
Summary: This study analyzed the pharmacokinetics, pharmacodynamics, safety, and efficacy of crizanlizumab in patients with sickle cell disease. The results demonstrated the sustained efficacy and long-term safety of the drug in treating sickle cell disease.
Article
Microbiology
Thomas P. Lodise, Scott Van Wart, Zoe M. Sund, Adam M. Bressler, Akram Khan, Amy T. Makley, Yasir Hamad, Robert A. Salata, Fernanda P. Silveira, Matthew D. Sims, Badih A. Kabchi, Mohamed A. Saad, Carrie Brown, Randolph E. Oler, Vance Fowler, Richard G. Wunderink
Summary: This multicenter study investigated the pharmacokinetics and pharmacokinetic-pharmacodynamic profile of intravenous minocycline in critically ill patients with MDR Acinetobacter baumannii infections. The study found that the dosing regimen of minocycline 200 mg i.v. every 12 hours may not be optimal for patients with MIC values of >1 mg/liter, requiring further clinical confirmation.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Oncology
Hanwen Wang, Huilin Ma, Richard J. Sove, Leisha A. Emens, Aleksander S. Popel
Summary: This study introduces a modular quantitative systems pharmacology (QSP) platform for predicting immunotherapy efficacy and identifying predictive biomarkers. Virtual clinical trials were conducted using a virtual patient cohort generated by the model, with retrospective analysis and model validation based on clinical trial data.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Pharmacology & Pharmacy
Jill Barber, Zubida M. Al-Majdoub, Narciso Couto, Martyn Howard, Yasmine Elmorsi, Daniel Scotcher, Naved Alizai, Saskia de Wildt, Felix Stader, Armin Sepp, Amin Rostami-Hodjegan, Brahim Achour
Summary: Biologics, particularly those containing Fc, are influenced by the FcRn receptor and have complex pharmacokinetics and pharmacodynamics. This study used a systems-informed modelling approach to predict the fate of Fc-containing biologics. The FcRn receptor was quantified in human tissues and its expression was found to vary among different tissues and individuals. The study also demonstrated the potential use of FcRn mRNA in plasma-derived exosomes as a clinical tool. The predicted effects of FcRn abundance on exposure to Fc-conjugated biologics were consistent with clinical observations.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Vikas Kumar, Wilma van Rensburg, Jacky L. Snoep, Henrich H. Paradies, Christopher Borrageiro, Carmen de Villiers, Ramesh Singh, Khashti Ballabh Joshi, Marina Rautenbach
Summary: TpcC, a Trp-rich cyclodecapeptide, can oligomerize and form self-assembled nanoparticles in aqueous solutions. The solvent system of ethanol:water has an influence on TpcC self-assembly, with different structures observed based on ethanol concentration. The drying process from 20 to 50% ethanol resulted in polymorphic surface morphologies with various small nanoparticles, while drying from 75% ethanol led to highly facetted 3-D crystals. The TpcC nano-assemblies have potential applications in antimicrobial coatings, surface disinfectants, food packaging, and wound healing materials.
Article
Environmental Sciences
Zahid Hassan, Martin Braster, Wilfred F. M. Roling, Hans Westerhoff
Summary: Arsenate-reducing microorganisms can mobilize arsenic into groundwater. A cultivation-based metagenomic strategy was developed to infer actual activities and bridge the knowledge gap between cultivation-independent and cultivation-dependent analyses. This study clarifies the mechanism for arsenic mobilization and redistribution in rural drinking water wells and highlights the potential risks and the need for appropriate bioremediation strategies. Rating: 8/10.
GEOMICROBIOLOGY JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Jakub Witkowski, Sebastian Polak, Dariusz Pawelec, Zbigniew Rogulski
Summary: The development of in vitro/in vivo translational methods and a clinical trial framework are needed to identify optimal therapeutic conditions. In this study, PBPK/PD modelling and virtual clinical trial simulations were used to evaluate the efficacy of siremadlin, trametinib, and their combination in melanoma patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Pharmacology & Pharmacy
Eleftheria Tsakalozou, Khondoker Alam, Priyanka Ghosh, Jessica Spires, Sebastian Polak, Lanyan Fang, Srinivasa Sammeta, Ping Zhao, Sumit Arora, Sam G. G. Raney
Summary: This report discusses the challenges in developing generic drug products, particularly for locally acting topical dermatological products. It emphasizes the use of modeling and simulation methodologies to accelerate the development of these generics and provides relevant insights and discussions.
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY
(2023)
Article
Chemistry, Organic
Robert N. Goldberg, Robert T. Giessmann, Peter J. Halling, Carsten Kettner, Hans Westerhoff
Summary: The measurement of apparent equilibrium constants K ' for enzyme-catalyzed reactions involves critical details that cannot be neglected in order to avoid systematic errors. Interferences, impurities, and failure to achieve equilibrium are significant factors to consider. Careful reporting of results, including substance identification, reaction specification, reaction conditions, equilibrium constant definition, nomenclature, symbols, units, and uncertainties, is of great importance. This document provides a general discussion on various aspects of equilibrium measurements and STRENDA recommendations regarding the measurements and reporting of results.
BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Jadwiga Kalicinska, Barbara Wisniowska, Sebastian Polak, Radoslaw Spiewak
Summary: The aim of this study was to develop an in silico model to predict the sensitizing potential of cosmetic ingredients based on their physicochemical characteristics. The model was compared to animal data and in vitro studies. The best-performing model achieved an accuracy of 86%, sensitivity of 80%, and specificity of 90% and successfully predicted the sensitizing potential of 7 out of 15 haptens. In conclusion, in silico models are a useful and ethical alternative to animal testing in assessing the safety of cosmetics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Endocrinology & Metabolism
Yanhua Liu, Hans V. Westerhoff
Summary: Inborn error of metabolism phenylketonuria (PKU) is typically caused by inactivation of phenylalanine hydroxylase (PAH). The reduced PAH activity results in elevated phenylalanine levels and phenylpyruvate in urine. Flux balance analysis (FBA) predicts reduced growth rate in PKU, unless tyrosine is supplemented. However, the PKU phenotype is brain-specific and can be treated by phenylalanine reduction instead of tyrosine supplementation. This study presents an extended FBA model that explains the brain specificity of the disease, the role of phenylpyruvate as a biomarker, the effect of excess phenylalanine on brain pathology, and the superiority of phenylalanine deprivation as therapy.
JOURNAL OF INHERITED METABOLIC DISEASE
(2023)
Article
Mathematics
Hans V. V. Westerhoff
Summary: Dynamic variables in non-equilibrium systems of life are determined by catalytic activities, which are related to genome expression. Modulating gene expression or enzyme function through medicinal drugs is becoming increasingly important. Despite the complexity of cellular systems biology, there are simple principles guiding the control of variables such as fluxes, concentrations, and half-times. By using time-unit invariance, a multitude of laws governing the control coefficients of multiple variables by all catalytic activities can be derived. The control of these variables is determined by time, resulting in simple integer sums when the variables are at maximum, minimum, or steady states.
Article
Multidisciplinary Sciences
Barbara Wisniowska, Susanne Linke, Sebastian Polak, Zofia Bielecka, Andreas Luch, Ralph Pirow
Summary: This paragraph mainly explains abbreviations related to drug metabolism and clearance, including parameters and indicators such as absorption, distribution, metabolism, and excretion.
Article
Biology
David D. van Niekerk, Erik Rust, Frank Bruggeman, Hans V. Westerhoff, Jacky L. Snoep
Summary: By analyzing models from the JWS Online and Biomodels databases, we investigated the use of the disequilibrium ratio as an estimator for the flux control of a reaction. While no functional relationship was found, the disequilibrium ratio can still be used as an estimator for the maximal flux control of a reaction step. We further expanded the analysis by incorporating the overall pathway disequilibrium ratio in the expression, leading to explicit expressions for flux control coefficients.
Article
Physics, Multidisciplinary
Yanfei Zhang, Hans V. Westerhoff
Summary: Confronted with unfavorable output processes, free-energy transducers can shift to lower gears to reduce output per unit input. This option is well-known in machines but not appreciated in biology. This study extends thermodynamic principles to explain biological gear shifting and identifies mechanisms. It shows that gear shifting optimizes performance in living systems, allowing them to switch to catabolic pathways with lower ATP stoichiometry, thereby increasing ATP synthesis flux and ensuring continued growth even in challenging conditions.
Article
Pharmacology & Pharmacy
Marcela Staniszewska, Michal Romanski, Sebastian Polak, Grzegorz Garbacz, Justyna Dobosz, Daria Myslitska, Svitlana Romanova, Jadwiga Paszkowska, Dorota Danielak
Summary: This study combines a novel dissolution apparatus with the design of experiments (DoE) and machine learning (ML) to overcome the challenge of recreating the substantial variability of gastric motility in drug dissolution experiments. The results demonstrate that this method can reasonably simulate dissolution profiles under different intragastric stress conditions.
Article
Mathematical & Computational Biology
Yanhua Liu, Hans V. Westerhoff
Summary: This study develops a method called 'dynamic competition Flux Balance Analysis' (dcFBA), which can accommodate changes in cell density caused by competition. The experiment shows that signal transduction between cells is crucial for the co-existence of diverse cell types in multicellular organisms. Moreover, mutants that lose social characteristics can outgrow other cells, suggesting that 'asocialness' rather than enhanced growth rates may characterize cancer cells and organisms causing ecological blooms.
NPJ SYSTEMS BIOLOGY AND APPLICATIONS
(2023)
Article
Biology
Joost W. Aerts, Serban M. Sarbu, Traian Brad, Pascale Ehrenfreund, Hans V. Westerhoff
Summary: Movile Cave is a unique and challenging ecosystem where specialized prokaryotic communities can adapt to different subenvironments and respond to environmental changes in a relatively short time.
Article
Biology
Frank J. Bruggeman, Maaike Remeijer, Maarten Droste, Luis Salinas, Meike Wortel, Robert Planque, Herbert M. Sauro, Bas Teusink, Hans Westerhoff
Summary: This paper extends the scope of metabolic control analysis (MCA) to a whole-cell context, considering metabolism in the evolutionary context of growth-rate maximisation. The study shows that elementary flux modes (EFMs) naturally emerge as optimal metabolic networks in this context, and their control properties can be derived. The paper also demonstrates the estimation of flux control coefficients from proteomics and ribosome-profiling data. The findings provide insights into the control of metabolic enzymes on growth rate and contribute to the understanding of general principles in cell biochemistry.