Article
Oncology
S. L. Groenland, R. A. G. van Eerden, K. Westerdijk, M. Meertens, S. L. W. Koolen, D. J. A. R. Moes, N. de Vries, H. Rosing, H. Otten, A. J. E. Vulink, I. M. E. Desar, A. L. T. Imholz, H. Gelderblom, N. P. van Erp, J. H. Beijnen, R. H. J. Mathijssen, A. D. R. Huitema, N. Steeghs, Dutch Pharmacology Oncology Grp DPOG
Summary: Pharmacokinetically guided dose optimization of oral targeted therapies is feasible in clinical practice and significantly reduces the proportion of underexposed patients.
ANNALS OF ONCOLOGY
(2022)
Article
Oncology
Mina Nikanjam, Shumei Kato, Jason K. Sicklick, Razelle Kurzrock
Summary: The objective of oncology therapeutics is to give the right drug(s) to the right patient at the right time. However, finding the right dose for each patient is a major challenge. Traditionally, cancer drugs are dosed based on a flat dose or dose based on surface area/weight, but patients' ability to tolerate drugs is influenced by multiple factors. Therefore, individualized drug dosing can improve the safety and effectiveness of treatment.
EUROPEAN JOURNAL OF CANCER
(2023)
Review
Biochemistry & Molecular Biology
Elettra Barberis, Shahzaib Khoso, Antonio Sica, Marco Falasca, Alessandra Gennari, Francesco Dondero, Antreas Afantitis, Marcello Manfredi
Summary: This review discusses the application of recent technological innovations in mass spectrometry to metabolomics analysis, with a focus on the use of artificial intelligence (AI) strategies. The article also explores the challenges and limitations of implementing metabolomics-AI systems, as well as recent tools and studies in disease classification and biomarker identification.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Alessia Vignoli, Emanuela Risi, Amelia McCartney, Ilenia Migliaccio, Erica Moretti, Luca Malorni, Claudio Luchinat, Laura Biganzoli, Leonardo Tenori
Summary: Precision oncology focuses on selecting the optimal therapy for individual patients with breast cancer, who need appropriate stratification for maximizing survival and quality of life. Gene-expression tools assist in estimating risk and benefit from chemotherapy, while NMR metabolomics has shown promising results in BC research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Medicine, General & Internal
Jacqueline So, Ann-Sophie De Craemer, Dirk Elewaut, Lai-Shan Tam
Summary: This article discusses the complex pathophysiology of spondyloarthritis (SpA) and the variability of treatment response. Genomic and microbiomic studies have identified important genes and the role of gut microbiome in the development of SpA. Exploring the link between gut microbiome and joint inflammation in SpA may provide potential biomarkers for treatment response prediction. Novel strategies targeting dysbiosis in SpA are also summarized. This represents a significant step toward precision medicine for patients with SpA.
FRONTIERS IN MEDICINE
(2022)
Review
Pharmacology & Pharmacy
Melissa J. J. Ankravs, Cathrine A. A. McKenzie, Michael T. T. Kenes
Summary: The understanding of delirium in critical illness has expanded, revealing its complexity and detrimental outcomes. Various risk factors contribute to the development of delirium, including age, frailty, medication exposure or withdrawal, sedation depth, and sepsis. Refinement in the categorization of delirium subtypes and the study of clinical phenotypes can help identify modifiable targets for improving outcomes.
Review
Pharmacology & Pharmacy
Guofang Shen, Kao Tang Ying Moua, Kathryn Perkins, Deron Johnson, Arthur Li, Peter Curtin, Wei Gao, Jeannine S. McCune
Summary: Sirolimus, a mTOR inhibitor, is prescribed to treat various diseases in children. Precision dosing through therapeutic drug monitoring is the current standard of care, but variability in pharmacokinetics, toxicity, and effectiveness still exists. Model-informed precision dosing and pharmacogenomic tools should be further explored. Point-of-care quantitation of sirolimus using dried blood spots is not recommended.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Chemistry, Multidisciplinary
Wendy Wei Gan, Lai Wah Chan, Wenji Li, Tin Wui Wong
Summary: Active targeting strategy is used in nanomedicine for cancer treatment. Personalization of nanomedicine based on patients' omics profiles faces challenges in ligand and matrix material selection. Past research shows that the selection of nanoparticulate ligands and matrix materials does not consider patients' cancer omics. Omics analysis of individual metabolizing enzymes and cancer cell surface receptors can aid in the selection of ligands and matrix materials for nanomedicine development.
JOURNAL OF CONTROLLED RELEASE
(2022)
Review
Pharmacology & Pharmacy
Tom C. Zwart, Henk-Jan Guchelaar, Paul J. M. van der Boog, Jesse J. Swen, Teun van Gelder, Johan W. de Fijter, Dirk Jan A. R. Moes
Summary: Immunosuppressive therapy is crucial for sustained allograft and patient survival after renal transplantation. However, variability in pharmacokinetics between patients and within patients poses challenges for optimal dosing, necessitating personalized dosing strategies to optimize outcomes. Pharmacometrics offers mathematical modeling to describe and quantify this variability, guiding dosing of immunosuppressants in modern renal transplantation.
DRUG DISCOVERY TODAY
(2021)
Article
Nutrition & Dietetics
Karin Amrein, Jessica A. Lasky-Su, Harald Dobnig, Kenneth B. Christopher
Summary: The study found that in critically ill patients, an increase in 25-hydroxyvitamin D levels following high dose vitamin D3 intervention is associated with favorable changes in various metabolomic profiles, including those involved in endothelial protection, enhanced innate immunity, and improved mitochondrial function.
CLINICAL NUTRITION
(2021)
Article
Clinical Neurology
Jose de Leon
Summary: This short communication discusses the importance of personalized dosing in psychiatry and provides a maintenance dosing table for three oral antipsychotics. Personalized dosing can be achieved by adjusting drug dosage according to individual needs based on dose-correction factors generated by pharmacokinetic studies.
EUROPEAN NEUROPSYCHOPHARMACOLOGY
(2022)
Review
Critical Care Medicine
Brian L. Erstad, Jeffrey F. Barletta
Summary: This paper discusses the impact of pharmacokinetic changes in obese patients on medication dosing in the intensive care unit. For hemodynamic support medications, a similar dosing strategy as in non-obese patients can be used. Medications for stress ulcer prophylaxis typically do not need dose adjustments. Anticoagulants for venous thromboembolism prophylaxis, however, require individualized dosing with higher doses in obese patients.
Article
Polymer Science
Weiguang Bai, Yongjin Hu, Jinghua Zhao, Liuqi Shi, Chunhua Ge, Zhiyuan Zhu, Jingyi Rao
Summary: The lack of progress in antibiotic development, particularly against intrinsically resistant Gram-negative pathogens with outer membranes, poses a global antibiotic crisis. To address this, a hypoxia-responsive nanoparticle (NP) is developed to encapsulate a hydrophobic antibiotic and a cationic potentiator. The release of both antibiotics and potentiators can be regulated in response to the severity of bacterial-induced hypoxia, allowing for precision antimicrobial dosing. The NP formulation demonstrates significant reduction in antibiotic dose and efficacy in eliminating planktonic and biofilm bacteria, offering a promising strategy to treat Gram-negative bacterial infections.
Review
Pharmacology & Pharmacy
Paula Del Valle-Moreno, Paloma Suarez-Casillas, Marta Mejias-Trueba, Pablo Ciudad-Gutierrez, Ana Belen Guisado-Gil, Maria Victoria Gil-Navarro, Laura Herrera-Hidalgo
Summary: This study reviewed and summarized the available evidence on Model-informed precision dosing (MIPD) software tools. A total of 28 software tools were identified, with 10 currently unavailable. The remaining 18 software tools were described in detail. These tools have significant applications in clinical practice, but standardization and validation are still needed.
Review
Infectious Diseases
Nynke G. L. Jager, Ming G. Chai, Reiner M. van Hest, Jeffrey Lipman, Jason A. Roberts, Menino O. Cotta
Summary: Precision dosing programs are valuable tools for optimizing antimicrobial dosing, but selecting the right program for local application can be difficult due to the diverse characteristics of available programs. This study identified 18 programs and described their features, including the ability to provide dosing support for beta-lactam drugs. Pharmacokinetic models combined with Bayesian statistics were commonly used to generate dosing recommendations. The findings highlight the variability among dosing software programs and emphasize the importance of clinicians assessing potential programs to meet their specific requirements.
CLINICAL MICROBIOLOGY AND INFECTION
(2022)
Article
Critical Care Medicine
Brian E. Driver, Matthew E. Prekker, Emily Wagner, Jon B. Cole, Michael A. Puskarich, Jamie Stang, Paige DeVries, Ellen Maruggi, James R. Miner
Summary: Among patients who underwent emergency tracheal intubation and mechanical ventilation, approximately 7.4% of patients may recall the awareness during paralysis, and a decreased level of consciousness prior to intubation is associated with this outcome.
Article
Immunology
David R. Boulware, Thomas A. Murray, Jennifer L. Proper, Christopher J. Tignanelli, John B. Buse, David M. Liebovitz, Jacinda M. Nicklas, Kenneth Cohen, Michael A. Puskarich, Hrishikesh K. Belani, Lianne K. Siegel, Nichole R. Klatt, David J. Odde, Amy B. Karger, Nicholas E. Ingraham, Katrina M. Hartman, Via Rao, Aubrey A. Hagen, Barkha Patel, Sarah L. Fenno, Nandini Avula, Neha Reddy, Spencer M. Erickson, Sarah Lindberg, Regina Fricton, Samuel Lee, Adnin Zaman, Hanna G. Saveraid, Walker J. Tordsen, Matthew F. Pullen, Nancy E. Sherwood, Jared D. Huling, Carolyn T. Bramante
Summary: SARS-CoV-2 vaccine-boosted participants experienced the least severe symptoms during COVID-19, and their symptoms improved the fastest over time. Vaccination against SARS-CoV-2 was found to be associated with reduced symptom severity in a sample of low to moderate risk adults enrolled in an outpatient COVID-19 treatment trial. Booster shots further reduced symptom severity.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Immunology
Manjunath P. Pai, Pier Giorgio Cojutti, Valentina Gerussi, Paola Della Siega, Carlo Tascini, Federico Pea
Summary: Linezolid-induced myelosuppression is likely to occur in cardiosurgical patients due to reduced kidney function and potential drug interactions. Population modeling and simulation demonstrate that lower doses coupled with therapeutic drug monitoring are necessary in this vulnerable population. Thus, reducing the empiric linezolid doses in cardiosurgical patients may help avoid toxicities, and further studies are needed to verify potential drug interactions.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Pharmacology & Pharmacy
Manjunath P. Pai, Sirima Sitaruno, Mohamed Abdelnabi
Summary: This study examined the precision gain or loss in drug dosing with estimated creatinine clearance (eCLcr) and estimated glomerular filtration rate (eGFR) using serum creatinine (eGFRcr) with and without race and body surface area (BSA) indexation. The results showed that the eGFR equation without race and BSA indexation provided a better method for drug dosing in terms of precision.
Editorial Material
Respiratory System
Kale S. Bongers, Kathleen A. Stringer, Robert P. Dickson
EUROPEAN RESPIRATORY JOURNAL
(2023)
Article
Infectious Diseases
Carolyn T. Bramante, John B. Buse, David M. Liebovitz, Jacinda M. Nicklas, Michael A. Puskarich, Ken Cohen, Hrishikesh K. Belani, Blake J. Anderson, Jared D. Huling, Christopher J. Tignanelli, Jennifer L. Thompson, Matthew Pullen, Esteban Lemus Wirtz, Lianne K. Siegel, Jennifer L. Proper, David J. Odde, Nichole R. Klatt, Nancy E. Sherwood, Sarah M. Lindberg, Amy B. Karger, Kenneth B. Beckman, Spencer M. Erickson, Sarah L. Fenno, Katrina M. Hartman, Michael R. Rose, Tanvi Mehta, Barkha Patel, Gwendolyn Griffiths, Neeta S. Bhat, Thomas A. Murray
Summary: This study aimed to evaluate the potential of outpatient COVID-19 treatment with metformin, ivermectin, or fluvoxamine to reduce the risk of long COVID. The findings showed that metformin treatment was associated with a 41% reduction in the incidence of long COVID compared to placebo, while ivermectin and fluvoxamine did not have the same effect.
LANCET INFECTIOUS DISEASES
(2023)
Article
Biochemistry & Molecular Biology
Jennifer Diaz-Espinosa, Kathleen A. A. Stringer, Gus R. R. Rosania
Summary: Mitochondrial health declines with age, making older patients more susceptible to adverse drug reactions. This study investigated the effectiveness of l-carnitine and acetylcarnitine as biomarkers for age-related, drug-induced changes in mitochondrial metabolism. The results showed that drug-induced alterations in mitochondrial metabolism were not reflected in the blood by l-carnitine or acetylcarnitine levels, suggesting that changes in muscle function may be more relevant for identifying individuals at increased risk for adverse drug reactions.
Article
Microbiology
Ronald G. Hall, Shuhan Liu, William C. Putnam, Rajareddy Kallem, Tawanda Gumbo, Manjunath P. Pai
Summary: Echinocandins like anidulafungin are first-line therapies for candidemia and invasive candidiasis, but their dosing may be suboptimal in obese patients. This study aimed to evaluate the impact of body size on anidulafungin pharmacokinetics (PK) and found that a higher maintenance dose of anidulafungin is needed in larger adults to achieve the desired effect.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Medicine, General & Internal
Pratima Chowdary, Banwari Agarwal, Maria Rita Peralta, Sanjay Bhagani, Simon Lee, James Goldring, Marc Lipman, Emal Waqif, Mark Phillips, Helen Philippou, Jonathan H. Foley, Nicola J. Mutch, Robert A. S. Ariens, Kathleen A. Stringer, Federico Ricciardi, Marie Watissee, Derralynn Hughes, Amit Nathwani, Anne Riddell, David Patch, Jim Buckley, Mark De Neef, Rahul Dimber, Cecilia Diaz-Garcia, Honey Patel, Aarti Nandani, Upuli Dissanayake, Nick Chadwick, Ahmed A. A. M. M. Alkhatip, Peter Watkinson, Eamon Raith, Suveer Singh, Tony Wolff, Rajeev Jha, Simon E. Brill, Ameet Bakhai, Alison Evans, Farhat Gilani, Keith Gomez
Summary: Nebulized recombinant tissue plasminogen activator (rt-PA) has the potential to improve lung injury and oxygenation in COVID-19 patients. Preliminary studies show better outcomes in patients receiving non-invasive respiratory support (NIRS). Randomized clinical trials are needed to confirm the clinical effects.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Pharmacology & Pharmacy
Jennifer Diaz-Espinosa, Austin Zhou, Kathleen A. Stringer, Gus R. Rosania, Gus R. Rosania
Summary: A study found that the antimycobacterial drug clofazimine (CFZ) accumulates in the spleen and other organs without increasing its concentration in the blood. The spleen plays a crucial role in modulating drug-induced inflammation and affecting the overall effect on the immune system.
Article
Biochemical Research Methods
John Takyi-Williams, Abbie D. Leino, Ruiting Li, Kevin J. Downes, Athena F. Zuppa, Amanda Bwint, Bo Wen, Duxin Sun, Marc H. Scheetz, Manjunath P. Pai
Summary: This study developed a bioanalytical method for the simultaneous quantification of multiple antibiotics from VAMS, which can facilitate pharmacokinetic/pharmacodynamic studies.