Review
Medicine, Research & Experimental
Joshuaine Grant, Fei Hua, Joshua F. Apgar, John M. Burke, Diana H. Marcantonio
Summary: The early assessment of dosing requirements is crucial in the development of biotherapeutics. If a high dose is needed for desired efficacy, it may not be feasible or commercially viable to develop the drug unless measures are taken to increase concentration or yield. Understanding the impact of target selection, drug format, and properties on dosing requirements can inform early decisions.
Article
Biotechnology & Applied Microbiology
Javier Martinez-Reina, Jose Luis Calvo-Gallego, Madge Martin, Peter Pivonka
Summary: The study found that Denosumab treatment for postmenopausal osteoporosis can effectively increase bone mineral density, but discontinuation can lead to rapid bone loss and increased bone tissue damage. The inclusion of a variable osteoclast precursor pool in BPMs models is essential for predicting the changes in osteoclast numbers. The effectiveness of Dmab treatment is weaker in patients with higher body weight, but bone loss after discontinuation is less pronounced in these patients.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Microbiology
Xia Xiao, Weixuan Lan, Yaqin Zhao, Ruichao Li, Yuan Liu, Juan Liu, Zhiqiang Wang
Summary: PK/PD modeling and Monte Carlo simulations were used to predict the efficacy of florfenicol against Pasteurella multocida strains in ducks. The optimal PK/PD parameter was determined, and a rational dosage regimen was suggested for different strains of P. multocida. Additionally, the PK/PD cutoff values for florfenicol against P. multocida were provided for the current marketed dose and the predicted daily dose in mainland China.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Engineering, Biomedical
Javier Martinez-Reina, Jose Luis Calvo-Gallego, Peter Pivonka
Summary: Drug holidays for postmenopausal osteoporosis patients treated with denosumab may lead to relapse of bone resorption and loss of bone density. Resuming treatment effectively restores bone density, but there is a potential risk of fractures during the drug holiday that needs to be considered.
JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS
(2021)
Article
Pharmacology & Pharmacy
Muhammad Kashif Maan, Tamoor Hamid Chaudhry, Adeel Sattar, Muhammad Abu Bakr Shabbir, Saeed Ahmed, Kun Mi, Waqas Ahmed, Shuyu Xie, Li Xin, Lingli Huang
Summary: Combining different drugs with various target sites is a new treatment approach for resistant bacteria, but finding the optimal dosage regimen is challenging. The study on aditoprim and sulfamethoxazole combination showed significant synergistic antimicrobial effects against T. Pyogenes isolates.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Jie Shao, Yaning Wang, Guenther Hochhaus
Summary: A semi-mechanistic PK/PD model was developed to describe the pulmonary targeting of BDP and BMP in rats. Results showed higher receptor occupancies in the lung after pulmonary delivery, and simulations indicated that slow dissolution rate and low permeability can improve pulmonary targeting.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Biotechnology & Applied Microbiology
Jose L. Calvo-Gallego, Peter Pivonka, Rocio Ruiz-Lozano, Javier Martinez-Reina
Summary: In this study, a pharmacokinetic (PK) model and pharmacokinetic-pharmacodynamic (PK-PD) model were developed for alendronate to predict bone density gain (BDG) in the treatment of postmenopausal osteoporosis (PMO). The results showed that at least three compartments are required to simulate the effect of alendronate in both short and long-term treatments. Clinical data reproduced by the PK-PD model demonstrated site-specific bone response, with 7% BDG at the hip and 4% BDG at the lumbar spine. Differences in BDG between sites were attributed to variations in bone-specific surface and porosity.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Infectious Diseases
Anxiong Huang, Feng Mao, Lingli Huang, Shuyu Xie, Yuanhu Pan, Wei Qu, Guyue Cheng, Zhenli Liu, Zonghui Yuan, Dapeng Peng, Haihong Hao
Summary: This study developed a dosing regimen for acetylkitasamycin to treat Streptococcus suis infection through pharmacokinetic-pharmacodynamic modeling. The regimen can effectively treat the infection and slow down the emergence of drug resistance.
Review
Chemistry, Multidisciplinary
Derek W. Bartlett, Adam M. Gilbert
Summary: Targeted protein degradation has emerged as an exciting area for therapeutic development in the pharmaceutical industry. This review provides practical insights for understanding the pharmacokinetic and pharmacodynamic properties of protein degraders, and offers a roadmap for their translational development. By using quantitative mathematical frameworks and standard experimental assays, this review highlights the unique characteristics of protein degraders and their potential in drug development.
CHEMICAL SOCIETY REVIEWS
(2022)
Article
Veterinary Sciences
Honglei Wang, Chen Chen, Xiaojie Chen, Jingju Zhang, Yiming Liu, Xiubo Li
Summary: This study used a mouse mastitis model to examine the effective dosage of rifaximin for treating mastitis in dairy cows caused by Staphylococcus aureus. It was found that the antibacterial effect of rifaximin was influenced by drug concentration and dosing interval, with optimal efficacy achieved when AUC(24)/MIC reached a certain value.
FRONTIERS IN VETERINARY SCIENCE
(2021)
Article
Infectious Diseases
Sazlyna Mohd Sazlly Lim, Aaron J. Heffernan, Hosam M. Zowawi, Jason A. Roberts, Fekade B. Sime
Summary: This study explored the potential efficacy of meropenem-sulbactam combination (MEM/SUL) against carbapenem-resistant Acinetobacter baumannii (CR-AB) infections. The combination demonstrated synergistic killing against a significant portion of clinical CR-AB isolates, with sulbactam driving the effect and meropenem acting as a potentiator. Monte Carlo simulations suggested that MEM/SUL regimen may be more effective in reducing bacterial burden compared to monotherapy in some cases.
EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES
(2021)
Article
Medicine, Research & Experimental
Maria Myzithras, Siqi Lin, Legairre Radden, Cynthia Hess Kenny, Zheng Cai, Angus MacDonald, Ralph Binetti, Michael Marlow, Paul Fracasso, Glenn Gibson, Christina Bartlett, Julie Hawkins, Steven Hansel
Summary: An in-house antibody generation campaign successfully developed a novel ultra-sensitive target engagement assay for IL-11 and established baseline levels of IL-11. This has significant implications for drug development and preclinical research.
Article
Pharmacology & Pharmacy
Robin Thomas Ulrich Haid, Andreas Reichel
Summary: The field of targeted protein degradation is rapidly growing, but there is a need for practical pharmacokinetic/pharmacodynamic models. Therefore, a comprehensive modeling framework has been developed to evaluate PROTACs, guide compound optimization, and connect degradation to downstream pharmacodynamic effects. This framework includes unique features such as fitting the hook effect, quantifying target occupancy, and deconvoluting the effects of degradation and inhibition on pharmacodynamic response.
Review
Pharmacology & Pharmacy
Dias Permeisari
Summary: Acute kidney injury (AKI) is a common complication post-cardiopulmonary bypass (CPB) with a high incidence rate. Various interventions, both pharmacological and non-pharmacological, have been studied to reduce the occurrence of AKI post-CPB. This review focuses on several renal protector agents, including fenoldopam, furosemide, mannitol, nitric oxide, and N-Acetylcysteine amide, which have shown significant benefits in reducing the incidence of AKI post-CPB.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Fawaz Alasmari, Mohammed S. Alasmari, Hussa Mubarak Muwainea, Hatun A. Alomar, Abdullah F. Alasmari, Sary Alsanea, Aws Alshamsan, Muhammad F. Rasool, Faleh Alqahtani
Summary: In this study, a physiologically-based pharmacokinetic (PBPK) model was used as a tool for precision dosing to predict the biological exposure of ceftriaxone in healthy and chronic kidney disease patients. The model successfully described the pharmacokinetic behavior of ceftriaxone in both populations and suggested dose adjustments for patients with renal impairment.
FRONTIERS IN PHARMACOLOGY
(2023)