Article
Infectious Diseases
Sha He, Zeneng Cheng, Feifan Xie
Summary: This study evaluated the pharmacokinetic/pharmacodynamic (PK/PD) of the Hartford nomogram and its influence on gentamicin dosing in critically ill patients. The study found that the Hartford nomogram provided adequate gentamicin exposure in patients with MIC<=1 mg/L.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2022)
Article
Pharmacology & Pharmacy
Hinojal Zazo, Eduardo Lagarejos, Manuel Prado-Velasco, Sergio Sanchez-Herrero, Jenifer Serna, Almudena Rueda-Ferreiro, Ana Martin-Suarez, M. Victoria Calvo, Jonas Samuel Perez-Blanco, Jose M. Lanao
Summary: This study developed a physiologically-based pharmacokinetic (PBPK) model for gentamicin to explore dosing regimens in neonates. The model showed good predictive performance and demonstrated high efficacy and low toxicity in preterm and term neonates.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Jurij Aguiar Zdovc, Jurij Hanzel, Tina Kurent, Nejc Sever, Matic Kozelj, Natasa Smrekar, Gregor Novak, Borut Stabuc, Erwin Dreesen, Debby Thomas, Tomaz Vovk, Barbara Ostanek, David Drobne, Iztok Grabnar
Summary: The study developed a population PK-PD model for ustekinumab in Crohn's disease and found associations between certain patient characteristics and drug exposure. Model-based simulations showed that transitioning to 4-weekly subcutaneous maintenance dosing could improve remission rates for patients who did not achieve remission with standard dosing.
Review
Veterinary Sciences
Longfei Zhang, Hongbing Xie, Yongqiang Wang, Hongjuan Wang, Jianhe Hu, Gaiping Zhang
Summary: Pharmacokinetic/pharmacodynamic (PK/PD) integration models are used to investigate the antimicrobial activity characteristics of drugs targeting pathogenic bacteria through comprehensive analysis of the interactions between PK and PD parameters. PK/PD models have been widely applied in the development of new drugs, optimization of the dosage regimen, and prevention and treatment of drug-resistant bacteria.
FRONTIERS IN VETERINARY SCIENCE
(2022)
Article
Pediatrics
Marika A. de Hoop-Sommen, Joyce E. M. van der Heijden, Jolien J. M. Freriksen, Rick Greupink, Saskia N. de Wildt
Summary: This study developed dosing guidelines for neonatal and infant gentamicin using a physiologically-based pharmacokinetic (PBPK) modeling approach. The simulations showed that the current dosages need to be optimized to achieve recommended drug levels. These findings have important implications for clinical practice.
FRONTIERS IN PEDIATRICS
(2023)
Review
Pharmacology & Pharmacy
Hui-Yin Yow, Kayatri Govindaraju, Audrey Huili Lim, Nusaibah Abdul Rahim
Summary: In the era of Bad Bugs, No Drugs, optimizing antibiotic therapy against multi-drug resistant (MDR) pathogens is crucial. Mathematical modelling has played an important role in personalized antibiotic treatment.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Infectious Diseases
Hubert C. Chua, Andy Tse, Nicholas M. Smith, Kari A. Mergenhagen, Raymond Cha, Brian T. Tsuji
Summary: Antimicrobial pharmacokinetics/pharmacodynamics (PK/PD) principles and models play a crucial role in understanding antibiotic killing mechanisms and optimizing dosing regimens for clinical outcomes. Personalized dosing based on proper pharmacokinetic sampling can enhance efficacy and minimize toxicity, while the development of integrated mechanistic models can further improve individualized dosing regimens.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2021)
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)
Article
Fisheries
Kananuch Vasuntrarak, Supeecha Wittayalertpanya, Janenuj Wongtavatchai, Nipattra Suanpairintr
Summary: This study aimed to determine the pharmacokinetics of long-acting oxytetracycline (OTC-LA) after intraperitoneal (IP) administration in Nile tilapia broodstock. The study found that a single IP administration of OTC-LA at a dosage of 100 mg/kg body weight can provide plasma oxytetracycline levels to prevent the growth of resistant mutant subpopulation.
Article
Pharmacology & Pharmacy
Harshith Neeli, Nazeeh Hanna, Khaled Abduljalil, Jaclyn Cusumano, David R. Taft
Summary: Clinical studies in preterm neonates are rare due to ethical concerns and recruitment difficulties. Empirical dose selection for this population may not accurately predict drug kinetics, especially for gentamicin. Physiologically based pharmacokinetic-pharmacodynamic (PBPK-PD) modeling can support dosing decisions and predict antibacterial effects in preterm neonates. Results suggest that a higher dose administered every 36 hours may provide effective antibacterial therapy.
JOURNAL OF CLINICAL PHARMACOLOGY
(2021)
Article
Microbiology
Praneeth Jarugula, Ayse Akcan-Arikan, Flor Munoz-Rivas, Brady S. Moffett, Vijay Ivaturi, Danielle Rios
Summary: This study aimed to determine the optimal vancomycin starting dose regimens in infants <= 180 days of age to achieve the highest probability of target attainment with AUC(24) of >= 400. It also examined the relationship between serum creatinine and vancomycin clearance in neonates.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Infectious Diseases
Feifan Xie, Yan Wang, Yaru Peng, Zeneng Cheng, Sanwang Li
Summary: This study characterized the pharmacokinetics of tobramycin in critically ill patients and evaluated the appropriateness of the Hartford nomogram. Results showed that the nomogram is effective for infections with pathogen MICs of <= 1 mg/L but not for MICs of 2 mg/L. Extended dosing intervals may be necessary to minimize toxicity in critically ill patients with higher MICs.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2021)
Article
Gastroenterology & Hepatology
Carmelo Scarpignato, Colin W. Howden, Eckhard Leifke, Darcy J. Mulford, Gezim Lahu, Axel Facius, Richard Hunt
Summary: This study explored the relationship between vonoprazan exposure and intragastric pH using a pharmacokinetic/pharmacodynamic (PK/PD) model. The results showed that vonoprazan at doses of 20 mg once and twice daily effectively controlled gastric acid secretion, supporting the clinical efficacy data in patients with acid-related disorders.
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
(2023)
Review
Pharmacology & Pharmacy
Elizabeth Leung, Ryan L. Crass, Sarah C. J. Jorgensen, Sumit Raybardhan, Bradley J. Langford, W. Justin Moore, Nathaniel J. Rhodes
Summary: Tocilizumab is a promising treatment for COVID-19, but global shortages have raised concerns. Alternative dosing strategies, such as fixed or lower doses, could help conserve supply without compromising therapeutic benefits. However, more research is needed to understand the relationship between tocilizumab dose, exposure, and response in COVID-19 patients.
CLINICAL PHARMACOKINETICS
(2022)
Article
Biochemical Research Methods
Javiera Cortes-Rios, Ramon C. Hermida, Maria Rodriguez-Fernandez
Summary: Studies have shown that incorporating circadian rhythm into pharmacokinetic models allows for better prediction of the effect of antihypertensive medications on blood pressure. Furthermore, optimizing the timing of medication administration depends on specific therapeutic objectives, the type of medication, and the patient's blood pressure profile. Therefore, personalized chrono-pharmacological recommendations for hypertension treatment are important.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Biographical-Item
Pharmacology & Pharmacy
Vikram Sinha, Lena E. Friberg, Ping Zhao
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY
(2021)
Article
Oncology
Ana-Marija Grisic, Wenyuan Xiong, Lenaig Tanneau, Siv Jonsson, Lena E. Friberg, Mats O. Karlsson, Haiqing Dai, Jenny Zheng, Pascal Girard, Akash Khandelwal
Summary: This study developed a semi-mechanistic pharmacokinetic-tumor growth dynamics model to investigate the exposure response relationship for avelumab and the interaction between PK and TGD. The PK of avelumab was described by a two-compartment model with a positive association between clearance and tumor size, without additional time-varying clearance identified. TGD was described by first-order tumor growth/shrinkage rates, with the tumor shrinkage rate decreasing exponentially over time and negatively correlated with drug concentration.
CLINICAL CANCER RESEARCH
(2022)
Article
Infectious Diseases
Aikaterini Gkoufa, Tomas Sou, Ilias Karaiskos, Christina Routsi, Yu-Wei Lin, Mina Psichogiou, Spyros Zakynthinos, Helen Giamarellou, Jian Li, Lena E. Friberg
Summary: This study assessed the pharmacokinetics of nebulised colistin methanesulfonate (CMS) for the treatment of ventilator-associated pneumonia (VAP) and found that nebulised CMS can achieve high concentrations of formed colistin in the epithelial lining fluid (ELF) while maintaining lower concentrations in plasma.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2022)
Article
Infectious Diseases
Iris K. Minichmayr, Vincent Aranzana-Climent, Lena E. Friberg
Summary: Pharmacokinetic/pharmacodynamic (PKPD) models are valuable tools for characterizing and translating antibiotic effects. These models provide a more accurate description of the time course of antibiotic effects, considering mechanistic knowledge of pathogens and drugs. This review provides a comprehensive overview of previously published PKPD models, highlighting their details and main development purposes.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2022)
Article
Infectious Diseases
Chenyan Zhao, Anna Chirkova, Staffan Rosenborg, Rodrigo Palma Villar, Johan Lindberg, Sven N. Hobbie, Lena E. Friberg
Summary: The aim of this study was to conduct a population pharmacokinetic analysis of apramycin and predict an efficacious dose based on data from the Phase I trial. The results showed that an anticipated efficacious dose of 30 mg/kg daily could be used for further Phase II clinical trials.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2022)
Article
Infectious Diseases
Iris K. Minichmayr, Suzanne Kappetein, Margreke J. E. Brill, Lena E. Friberg
Summary: In this study, the impact of differently shaped clinical pharmacokinetic profiles of meropenem on the growth and killing patterns of Pseudomonas aeruginosa was investigated using a semi-mechanistic PKPD model and a PK/PD index-based approach. Continuous infusion plus loading dose and 3-hour infusions were found to be superior to standard 0.5-hour infusions in certain scenarios.
Article
Medicine, Research & Experimental
Maddalena Centanni, Abel Thijs, Ingrid Desar, Mats O. Karlsson, Lena E. Friberg
Summary: This study investigated the factors influencing blood pressure measurements and compared different measurement techniques using a pharmacokinetic-pharmacodynamic modeling framework. The study found that circadian changes, as well as random intra-day and inter-day variability, were the largest sources of within-individual variation in blood pressure. Continuous home-based measurements taken at a consistent time or within a limited time frame were found to provide the most consistent blood pressure estimates.
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2023)
Article
Pharmacology & Pharmacy
Sreenath M. Krishnan, Lena E. Friberg
Summary: This study investigates the impact of tumor follow-up data and estimation methods on the accuracy of tumor size metrics and predicted hazard of death for individual patients. The results indicate that TSRw6 and the model-predicted tumor time course have better forecasting properties than TTG or kG. The population pharmacokinetic parameters and data method perform similarly or better than individual PK parameters method in estimating individuals' hazard of death.
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Sreenath M. Krishnan, Lena E. Friberg, Francois Mercier, Rong Zhang, Ben Wu, Jin Y. Jin, Tien Hoang, Marcus Ballinger, Rene Bruno, Mats O. Karlsson
Summary: This study used data from the IMpower131 study to establish a multistate model framework and investigate the influence of second-line immunotherapies on overall survival analysis. The study found that high PD-L1 expression was associated with a decreased risk of progression, while the presence of liver metastasis indicated a high risk of disease progression. The simulations showed that the addition of atezolizumab to the treatment regimen improved patient survival significantly.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Pharmacology & Pharmacy
Robin J. Svensson, Qing Xi Ooi, Lena E. Friberg, Narendra Maharaj, Pramod Kumar Reddy, Luis Lopez-Lazaro, Emma Hansson
Summary: Dr. Reddy's Laboratories rituximab (DRL-RI) is a rituximab biosimilar that showed similar pharmacokinetic, pharmacodynamic, efficacy, safety, and immunogenicity profiles to the reference medicinal product MabThera. The study also indicated that tumor size may influence the pharmacokinetics of rituximab, but does not affect the evaluation of the drug product.
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Han Liu, Ana-Marija Milenkovic-Grisic, Sreenath M. Krishnan, Siv Joensson, Lena E. Friberg, Pascal Girard, Karthik Venkatakrishnan, Yulia Vugmeyster, Akash Khandelwal, Mats O. Karlsson
Summary: This study applies the multistate pharmacometric modeling and simulation framework to investigate the dose optimization of bintrafusp alfa in non-small cell lung cancer patients. A six-state multistate model is developed to describe the endpoints data, and the results suggest that the 1200 mg dose may lead to longer median overall survival compared to the 500 mg dose.
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Yaru Peng, Iris K. Minichmayr, Han Liu, Feifan Xie, Lena E. Friberg
Summary: This study used pharmacometric multistate modeling to investigate predictors of in-hospital mortality in critically ill patients treated with meropenem. The study found that creatinine clearance and the duration of unbound concentrations exceeding the minimum inhibitory concentration significantly influenced the transitions and survival outcome of the patients.
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Eman I. K. Ibrahim, Mats O. Karlsson, Lena E. Friberg
Summary: This study developed a semi-mechanistic pharmacokinetic-pharmacodynamic modeling framework to investigate the relationship between systemic exposure to ibrutinib and its efficacy and toxicity biomarkers. The simulations showed that lower dosing schedules can reduce the incidence of hypertension without compromising the reduction in tumor burden compared to the approved dosing schedule.
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Anders Thorsted, Anh Duc Pham, Lena E. Friberg, Elisabet I. Nielsen
Summary: Neutrophil granulocytes play a crucial role in the host's immune response against pathogens, and severe neutropenia can make individuals more vulnerable to infections. This study developed a mathematical model to characterize the kinetics of neutrophil-mediated bacterial killing and investigated the contribution of the immune system to the clearance of bacterial infections. The model successfully predicted data from both in vitro and in vivo studies and can be used to assess the capacity of the host immune response at an individual level.
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Javier Sanchez, Christina Claus, Rosmarie Albrecht, Brenda C. Gaillard, Joana Marinho, Christine Mcintyre, Tamara Tanos, Axel Boehnke, Lena E. Friberg, Siv Joensson, Nicolas Frances
Summary: This study characterizes the pharmacology of FAP-4-1BBL as a bispecific antibody and predicts the dose range for trimeric complex formation when combined with the T-cell engager cibisatamab using mathematical modeling techniques. It highlights the importance of mathematical modeling based on in vitro data in aiding dose selection.
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY
(2023)