Article
Pharmacology & Pharmacy
Jeanine E. Ballard, Parul S. Pall, Joshua Vardigan, Fuqiang Zhao, Marie A. Holahan, Xiaoping Zhou, Nina Jochnowitz, Richard L. Kraus, Rebecca M. Klein, Darrell A. Henze, Andrea K. Houghton, Christopher S. Burgey, Christopher Gibson, Arie Struyk
Summary: MK-2075 is a small-molecule selective inhibitor of the NaV1.7 channel investigated for postoperative pain treatment. A translational strategy was developed to quantitatively relate drug exposure, target modulation, and pharmacological response in preclinical animal models, informing clinical study design and decision criteria. Integration of pharmacokinetic and pharmacodynamic data from preclinical species guided dose prediction and target modulation assessment for potential clinical efficacy.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Meina Liang, Bing Wang, Amy Schneider, Inna Vainshtein, Lorin Roskos
Summary: Tovetumab, a fully human IgG2 monoclonal antibody, specifically binds to human PDGFR alpha and blocks signal transduction. Studies show that tovetumab competes with PDGF-AA for binding, indirectly measuring receptor occupancy and providing a novel PD biomarker approach.
Article
Pharmacology & Pharmacy
Morris Muliaditan, Oscar Della Pasqua
Summary: The study aims to develop a drug-disease model that distinguishes between drug- and system-specific properties, providing theoretical basis for the clinical application of anti-tubercular drugs.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Review
Pharmacology & Pharmacy
Kunyi Wu, Su-Young Choi, Kimberly Bergman, Shirley Seo
Summary: The FDA's Animal Rule provides a regulatory pathway for treating serious conditions caused by exposure to lethal agents, based on integrating clinical pharmacology evidence to determine effective human doses.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
Review
Pharmacology & Pharmacy
Kunyi Wu, Su-Young Choi, Kimberly Bergman, Shirley Seo
Summary: The Animal Rule provides a unique regulatory pathway for drugs intended to treat serious conditions caused by exposure to lethal agents when human efficacy studies are not ethical. Human dose selection under the Animal Rule is based on integrating clinical pharmacology evidence from in vitro, animal, and human studies.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
Review
Infectious Diseases
Bing Leng, Genquan Yan, Cuicui Wang, Chengwu Shen, Wen Zhang, Wei Wang
Summary: Tigecycline, a novel glycylcycline antibiotic, has shown promising efficacy against various micro-organisms, but concerns have been raised about its potential to increase all-cause mortality. Recommendations for higher dosages in treating serious infections should consider the drug's atypical protein binding property, and combination therapy with other antibiotics may help lower the MICs of multidrug-resistant bacteria.
JOURNAL OF GLOBAL ANTIMICROBIAL RESISTANCE
(2021)
Review
Microbiology
Christopher Witzany, Jens Rolff, Roland R. Regoes, Claudia Igler
Summary: The coupling of PKPD and population genetics models can be used to determine treatment regimens that minimize the potential for antimicrobial resistance evolution. This modeling framework enables the assessment of resistance evolution in response to dynamic selection pressures and provides a more comprehensive and realistic prediction of bacterial escape from antimicrobials.
Article
Microbiology
S. M. Bhavnani, M. Trang, D. C. Griffith, O. Lomovskaya, J. P. Hammel, J. S. Loutit, S. K. Cammarata, M. N. Dudley, P. G. Ambrose, C. M. Rubino
Summary: This study analyzed the pharmacokinetic-pharmacodynamic (PK-PD) target attainment of Meropenem-vaborbactam using population pharmacokinetic models, nonclinical PK-PD targets, in vitro surveillance data, and simulation. The results supported a specific dosing regimen and provided dosing adjustments for patients with renal impairment.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Review
Neurosciences
Caterina Paoli, Paulina Misztak, Giulia Mazzini, Laura Musazzi
Summary: This narrative review focuses on the association between changes in DNA methylation patterns and major depressive disorder (MDD) or depressive-like phenotype in animal models, as well as mechanisms of response to antidepressant drugs. The evidence collected suggests that DNA methylation could serve as a promising epigenetic biomarker of pathology and help predict the efficacy of antidepressant treatment. Moreover, specific changes in DNA methylation signature may play a role in the etiopathogenesis and induction of antidepressant effects.
CURRENT NEUROPHARMACOLOGY
(2022)
Article
Infectious Diseases
Emanuela Locci, Jiajun Liu, Gwendolyn M. Pais, Alberto Chighine, Dariusc Andrea Kahnamoei, Theodoros Xanthos, Athanasios Chalkias, Andrew Lee, Alan R. Hauser, Jack Chang, Nathaniel J. Rhodes, Ernesto d'Aloja, Marc H. Scheetz
Summary: This study investigates the potential kidney injury caused by Polymyxin B treatment and aims to detect it early through the analysis of urinary metabolites. The study found that the concentration of urinary taurine significantly increased on the first day of treatment and then returned to baseline levels. Taurine may serve as an early indicator of acute kidney damage caused by Polymyxin B.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2022)
Article
Multidisciplinary Sciences
E. A. Riddell, K. J. Iknayan, L. Hargrove, S. Tremor, J. L. Patton, R. Ramirez, B. O. Wolf, S. R. Beissinger
Summary: The study found that small mammal communities in the Mojave Desert remained relatively stable, while bird populations declined significantly in response to warming and drying. This difference in response may be attributed to the different microhabitat use of birds and mammals.
Article
Microbiology
Indy Sandaradura, Jessica Wojciechowski, Deborah J. E. Marriott, Richard O. Day, Sophie Stocker, Stephanie E. Reuter
Summary: Fluconazole exposure in critically ill patients is crucial, with model-optimized dosing showing better efficacy target attainment and less overexposure compared to guideline dosing. This suggests that individualized dosing strategies may be more beneficial in treating severe fungal infections.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Review
Oncology
Chaofeng Liang, Shuxin Huang, Yujie Zhao, Shaohua Chen, Yangqiu Li
Summary: TOX is a transcriptional factor containing the highly conserved HMG-box region, involved in maintaining tumors and promoting T cell exhaustion. It plays an important role in lymphocytic malignancies and may serve as a potential immune biomarker and target in immunotherapy for hematological malignancies.
BIOMARKER RESEARCH
(2021)
Article
Microbiology
Thanh Bach, Gregory A. Deye, Ellen E. Codd, John Horton, Patricia Winokur, Guohua An
Summary: Oxfendazole, a potent veterinary antiparasitic drug, is being developed for human use to treat various parasitic infections. Results from recent clinical trials showed that the pharmacokinetics of oxfendazole is nonlinear and affected by food, with mild effects on hemoglobin concentrations. Population pharmacokinetic-pharmacodynamic modeling was used to quantitatively characterize the relationship between oxfendazole dose, pharmacokinetics, and hemoglobin concentration, facilitating dose optimization for different patient populations with parasitic infections.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Microbiology
Jiao Xie, Qianting Yang, Xinyan Han, Yuzhu Dong, Tao Zhang, Youjia Li, Meixi Ji, Chenwei Liu, Yan Cai, Yan Wang
Summary: This study found that differences in pharmacokinetics/pharmacodynamics target attainment are often overlooked when antifungals are switched in critically ill patients. The results showed that triazoles at guideline-recommended doses could achieve target exposure for de-escalation treatment, while fluconazole and voriconazole performed poorly. Additionally, the achievement of target exposure for echinocandins decreased as body weight increased, with intermittent dosing strategy showing slightly higher CFR values in most simulations compared to conventional dosing strategy.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
