Article
Pharmacology & Pharmacy
Vivaswath S. Ayyar, Pharavee Jaiprasart, Brian Geist, Zheng Huang Devine, Martin Case, Anasuya Hazra, Chyi-Hung Hsu, Madhu Chintala, Weirong Wang
Summary: The study developed antigen-binding fragment (F-ab) reversal agents to reverse the anticoagulant effect of JNJ-64179375 (JNJ-9375) in bleeding emergencies. Three reversal agents of varying binding affinities to JNJ-9375 were tested in cynomolgus monkeys, showing different neutralization characteristics in vivo. The model-based approach helped select JNJ-67842125 as the most effective reversal agent for JNJ-9375 neutralization.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Microbiology
Kendra K. Radtke, Jacqueline P. Ernest, Nan Zhang, Nicole C. Ammerman, Eric Nuermberger, Robert Belknap, Rosanna Boyd, Timothy R. Sterling, Rada M. Savic
Summary: The study identified the optimal rifapentine dose for a 6-week monotherapy regimen and predicted clinical efficacy, suggesting that a 600-mg daily dose for 6wP may result in equal or better efficacy than 1HP and 3HP for LTBI treatment, without the potential added toxicity of isoniazid.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Review
Pharmacology & Pharmacy
Amelia R. Cossart, Nicole M. Isbel, Carla Scuderi, Scott B. Campbell, Christine E. Staatz
Summary: Age-related changes in physiology can affect drug metabolism and responsiveness, potentially requiring adjustments in drug dosing for elderly patients. Elderly kidney transplant recipients are at higher risk for complications, especially due to increased susceptibility to immunosuppressant side effects; however, current dosing and monitoring protocols may not account for age differences.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Amedeo De Nicolo, Giacomo Stroffolini, Miriam Antonucci, Jacopo Mula, Elisa Delia De Vivo, Jessica Cusato, Alice Palermiti, Giuseppe Cariti, Giovanni Di Perri, Silvia Corcione, Francesco Giuseppe De Rosa, Antonio D'Avolio
Summary: This study investigated the long-term plasma pharmacokinetics of dalbavancin in outpatients with ABSSSI or osteoarticular infections who were treated with either one or two doses of 1500 mg. The results showed that dalbavancin exposure exceeded previously suggested pharmacodynamic targets, indicating a need for optimization in the treatment of osteoarticular infections.
Article
Microbiology
Sean N. Avedissian, Gwendolyn Pais, Jiajun Liu, J. Nicholas O'Donnell, Thomas P. Lodise, Michael Neely, Walter C. Prozialeck, Peter C. Lamar, Leighton Becher, Marc H. Scheetz
Summary: The study identified that in a rat model, both the dosage and frequency of vancomycin administration significantly influenced the risk of kidney injury, with exposure-response relationships observed between pharmacokinetic exposure and kidney injury molecule-1 levels.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Review
Infectious Diseases
Semra Palic, Josh H. Beijnen, Thomas P. C. Dorlo
Summary: This review provides an update on the recent developments in the clinical pharmacology of miltefosine, including a discussion on its pharmacokinetics and pharmacodynamics, as well as the current dosing regimens.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2022)
Article
Pharmacology & Pharmacy
Amedeo De Nicolo, Michele Pinon, Alice Palermiti, Antonello Nonnato, Alessandra Manca, Jacopo Mula, Silvia Catalano, Francesco Tandoi, Renato Romagnoli, Antonio D'Avolio, Pier Luigi Calvo
Summary: The study aimed to describe the concentrations and variability of tacrolimus in whole blood and peripheral blood mononuclear cells (PBMC) in pediatric patients undergoing constant immunosuppressive maintenance therapy after liver transplantation. Variability in PBMC concentrations of tacrolimus was similar to the variability in whole blood, with weight-adjusted dose and age appearing as significant predictors of concentrations in both compartments. Seasonal variation of tacrolimus concentrations was observed in whole blood but not in PBMC within the same individual patients.
FRONTIERS IN PHARMACOLOGY
(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
Surgery
Grace Lassiter, Ryo Otsuka, Takayuki Hirose, Ivy Rosales, Ahmad Karadagi, Toshihide Tomosugi, Abbas Dehnadi, Hang Lee, Robert B. Colvin, Jason Baardsnes, Anna Moraitis, Emma E. Smith, Zahida Ali, Phil Berhe, Andrew Mulder, Bernd Meibohm, Bruce Daugherty, Siobhan Fogarty, Richard N. Pierson, Seth Lederman, Tatsuo Kawai
Summary: TNX-1500, a modified anti-CD154 monoclonal antibody, effectively prevents kidney allograft rejection without causing platelet activation, thus avoiding previously identified thrombotic complications associated with this pathway.
AMERICAN JOURNAL OF TRANSPLANTATION
(2023)
Article
Medicine, General & Internal
Simeon Schietzel, Lia Bally, Grazia Cereghetti, Nicolas Faller, Matthias B. Moor, Bruno Vogt, Felix Rintelen, S. Trelle, Daniel Fuster
Summary: Kidney stones are a global healthcare problem, and effective medical prophylaxis for stone formers is still an unmet need. This study aims to evaluate the effect of empagliflozin on urinary supersaturations in non-diabetic kidney stone formers and assess its therapeutic potential for recurrence prevention.
Article
Agriculture, Dairy & Animal Science
Francesca De Santis, Andrea Boari, Francesco Dondi, Paolo Emidio Crisi
Summary: Chronic kidney disease is common in adult and aged dogs and cats, requiring lifelong medication to maintain quality of life; however, guidance and literature on drug dosage adjustment in dogs and cats with chronic kidney disease are often lacking.
Article
Infectious Diseases
Vincent Aranzana-Climent, Diarmaid Hughes, Sha Cao, Magdalena Tomczak, Malgorzata Urbas, Dorota Zabicka, Carina Vingsbo Lundberg, Jon Hansen, Johan Lindberg, Sven N. Hobbie, Lena E. Friberg
Summary: This study characterized the preclinical pharmacokinetics (PK) and pharmacodynamics of the drug candidate apramycin in fighting carbapenem-resistant gram-negative pathogens. A mathematical model was developed to predict human efficacy based on in vitro and in vivo data. Apramycin showed good lung penetration and the mathematical model integrated lung PK to drive mouse PK and pharmacodynamics. Apramycin was demonstrated as a candidate for treatment of carbapenem-resistant gram-negative pneumonia.
CLINICAL MICROBIOLOGY AND INFECTION
(2022)
Editorial Material
Anesthesiology
Talmage D. Egan
Summary: The drug titration paradox refers to the reversal of the expected dose-effect relationship when titrating a drug to a specified level of effect.
BRITISH JOURNAL OF ANAESTHESIA
(2022)
Article
Pharmacology & Pharmacy
Nicola Maseko, Siyao Yang, Chengcheng Li, Siqi Zhang, Ruiying Wang, Yawen Zhang, Chuanjiang Li, Chuanjie Zhang, Liang Li
Summary: The aim of this study was to analyze the effects of various genetic polymorphisms and clinical factors on tacrolimus (TAC) concentration in the convalescence period (CP) and stabilization period (SP) post-liver transplantation. Results showed that only five genetic polymorphisms were significantly associated with TAC concentration in the CP, and none showed significant association in the SP. The study also identified specific genes and clinical factors as independent predictors of TAC concentration in the CP.
Article
Pharmacology & Pharmacy
Pere Fontova, Helena Colom, Raul Rigo-Bonnin, Lisanne N. van Merendonk, Anna Vidal-Alabro, Nuria Montero, Edoardo Melilli, Maria Meneghini, Anna Manonelles, Josep M. Cruzado, Juan Torras, Josep Maria Grinyo, Oriol Bestard, Nuria Lloberas
Summary: The study compared the pharmacokinetic and pharmacodynamic profiles of tacrolimus between morning and night doses, showing significantly lower drug concentrations in whole blood and intracellular compartments after the night dose compared to the morning dose. However, this lower exposure did not translate into a significant reduction in pharmacodynamic effect.
FRONTIERS IN PHARMACOLOGY
(2021)