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
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
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
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)
Article
Pharmacology & Pharmacy
Li Xue, Qi Hui, Jin Fei, Yao Bu-Fan, Wu Yue-E, Qi Yu-Jie, Kou Chen, Wu Xi-Rong, Luo Xiao-Jing, Shen Yan-Hua, Zheng Xu, Wang Yong-Hong, Xu Fang, Jiao Wei-Wei, Li Jie-Qiong, Xiao Jing, Dong Yi-Ning, Du Bin, Shi Hai-Yan, Xu Bao-Ping, Shen A-Dong, Zhao Wei
Summary: By conducting a population pharmacokinetic study and recommending a model-based dosage regimen, this study aimed to optimize sepsis therapy in neonates and young infants using ceftazidime. Through Monte Carlo simulation, evidence-based dosage regimens were proposed based on developmental pharmacokinetic-pharmacodynamic analysis, covering the entire range of this vulnerable population.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
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
Microbiology
Sinenhlanhla Mtshali, Byron A. Jacobs
Summary: Physiologically based pharmacokinetic models have gained popularity in drug development and regulatory science. This study validates the model's effectiveness in predicting drug-drug interaction and the pharmacokinetics of antiretroviral and anti-TB drugs through mathematical solving and sensitivity analysis.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Review
Obstetrics & Gynecology
Sin Yin Lim, Jamie L. Miller
Summary: This article reviews the dosing recommendations and safety of ampicillin in neonates, and finds that the dosing recommendations for ampicillin in the treatment of group B streptococcal infection are well-supported, but the dosing recommendations for meningitis lack supporting evidence.
AMERICAN JOURNAL OF PERINATOLOGY
(2022)
Review
Pharmacology & Pharmacy
Joseph A. Piscatelli, Jisun Ban, Andrew T. Lucas, William C. Zamboni
Summary: Major developments in nanomedicines, such as nanoparticles and conjugates, have revolutionized drug delivery capabilities, but there is considerable inter-patient variability seen in the systemic disposition, tumor delivery, and pharmacological effects of NP agents. Evaluating fundamental factors influencing NP disposition is crucial for clinical development.
Review
Pharmacology & Pharmacy
Dermot Cox
Summary: Despite the immense potential integrins hold in medicine, the investment in anti-integrin drug discovery programs has yielded little results so far. The main reasons for this are the toxicity and limited efficacy of these drugs, as well as the complex pathophysiology of integrins making drug development challenging.
EXPERT OPINION ON DRUG DISCOVERY
(2021)
Article
Pharmacology & Pharmacy
Shuai-Bing Liu, Xia Yao, Jun Tao, Jian-Jun Yang, Ying-Ying Zhao, Dong-Wei Liu, Su-Yun Wang, Su-Ke Sun, Xu Wang, Pang-Ke Yan, Nan Wu, Xiao Liu, Xiao-Jian Zhang, Xin Tian, Zhang-Suo Liu
Summary: The aim of this study was to develop a population pharmacokinetic (PK) model for ciprofol and its major metabolite M4, and link it to the population pharmacodynamics (PD) model in subjects with different renal functions. The study found that the PK of ciprofol and M4 could be best described by three-compartment and two-compartment models, respectively. The concentrations of ciprofol and M4 were linked using a linear protein binding model. Hemoglobin and uric acid were identified as covariates affecting the clearance of ciprofol and M4. The developed model provides a comprehensive understanding of the PK and PD of ciprofol.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Article
Infectious Diseases
Pierre Chauvelot, Celine Dupieux-Chabert, Lelia Abad, Aubin Souche, Tristan Ferry, Jerome Josse, Frederic Laurent, Florent Valour
Summary: The study demonstrated that dalbavancin has the ability to effectively eradicate intraosteoblastic reservoir of Staphylococcus aureus in bone and joint infections. It showed significant reduction in bacterial inoculum at both low concentration and standard therapeutic doses, with similar efficacy to vancomycin but less efficient than rifampicin. Dalbavancin was found to be the only molecule significantly active at a low concentration.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2021)
Editorial Material
Pharmacology & Pharmacy
Samira Samiee-Zafarghandy, John van den Anker, Karel Allegaert
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Article
Medicine, Research & Experimental
Katharine Cheng, Fenna Mahler, Irja Lutsar, Begonya Nafria Escalera, Stefanie Breitenstein, Gilles Vassal, Joana Claverol, Nuria Noel Palacio, Ron Portman, Gavin Pope, Martijn Bakker, Tessa van Der Geest, Mark A. A. Turner, Saskia N. N. de Wildt
Summary: Many medicines are used off-label in children outside the terms of the license. The Conect4children project aims to establish a pan-European pediatric clinical trial network to facilitate the development of new medicines for children. The project has successfully set up a multidisciplinary advice service, including the input of young patients and families, to optimize pediatric trial development and provide valuable advice to trial sponsors.
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2023)
Article
Pharmacology & Pharmacy
Evelina Cardoso, Anaelle Monfort, Ema Ferreira, Hedvig Nordeng, Ursula Winterfeld, Karel Allegaert, Peggy Gandia, Monia Guidi, Alice Panchaud
Summary: Human milk is the best nutrition for infants, and taking medication postpartum is common. Discontinuing breastfeeding is often wrongly advised due to concerns of adverse effects on the infant, even though only a few drugs are strictly prohibited while breastfeeding. Most drugs are transferred from the mother's blood to the milk, but the amount ingested by the infant is usually small. As there is limited population-based evidence on drug safety during breastfeeding, risk assessment relies on available clinical evidence, pharmacokinetic principles, and specialized sources of information for clinical decision-making. Risk assessment should consider both the potential risk to the infant and the benefits and risks associated with breastfeeding and maternal disease. Identifying situations with potential for drug accumulation in the infant is crucial for risk assessment. Healthcare providers should assume maternal concerns and utilize risk communication to ensure medication adherence without interrupting breastfeeding unnecessarily. Decision support algorithms and strategies can be used to minimize drug exposure in the breastfed infant, even when clinically not justified.
Article
Nutrition & Dietetics
Michael Ceulemans, Joline van de Vel, Dorine W. W. Swinkels, Coby M. M. Laarakkers, Jaak Billen, Kristel Van Calsteren, Karel Allegaert
Summary: This observational study aimed to provide the first data on cord blood hepcidin levels in a Belgian cohort and determine variables associated with cord blood hepcidin concentrations. The study found a moderate correlation between cord blood hepcidin and cord blood ferritin and hemoglobin, as well as an association with mode of delivery.
Review
Biochemistry & Molecular Biology
Evelina Cardoso, Monia Guidi, Nina Nauwelaerts, Hedvig Nordeng, Marie Teil, Karel Allegaert, Anne Smits, Peggy Gandia, Andrea Edginton, Shinya Ito, Pieter Annaert, Alice Panchaud
Summary: PBPK and popPK modeling are promising approaches to fill the gap in knowledge of medicine safety in breastfeeding, as illustrated with our escitalopram example. These methods can provide a more complete characterization of infant medicine exposure through human milk and simulate extreme situations while decreasing the burden of sampling in breastfeeding women.
EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY
(2023)
Article
Medicine, General & Internal
Mathias L. Hansen, Adelina Pellicer, Simon Hyttel-Srensen, Ebru Ergenekon, Tomasz Szczapa, Cornelia Hagmann, Gunnar Naulaers, Jonathan Mintzer, Monica Fumagalli, Gabriel Dimitriou, Eugene Dempsey, Jakub Tkaczyk, Guoqiang Cheng, Siv Fredly, Anne M. Heuchan, Gerhard Pichler, Hans Fuchs, Saudamini Nesargi, Gitte H. Hahn, Salvador Piris-Borregas, Jan Sirc, Miguel Alsina-Casanova, Martin Stocker, Hilal Ozkan, Kosmas Sarafidis, Andrew O. Hopper, Tanja Karen, Beata Rzepecka-Weglarz, Serife S. Oguz, Luis Arruza, Asli C. Memisoglu, Ruth del Rio Florentino, Mariana Baserga, Pierre Maton, Anita C. Truttmann, Isabel de las Cuevas, Peter Agergaard, Pamela Zafra, Lars Bender, Ryszard Lauterbach, Chantal Lecart, Julie de Buyst, Afif El-Khuffash, Anna Curley, Olalla O. Vaccarello, Jan Miletin, Evangelia Papathoma, Zachary Vesoulis, Giovanni Vento, Luc Cornette, Laura S. Lopez, Beril Yasa, Anja Klamer, Massimo Agosti, Olivier Baud, Emmanuele Mastretta, Merih Cetinkaya, Karen McCall, Shujuan Zeng, Eleftheria Hatzidaki, Agata Bargiel, Sylwia Marciniak, Xiaoyan Gao, Lin Huijia, Lina Chalak, Ling Yang, Shashidhar A. Rao, Xin Xu, Begona L. Gonzalez, Maria Wilinska, Zhaoqing Yin, Iwona Sadowska-Krawczenko, Itziar Serrano-Vinuales, Barbara Krolak-Olejnik, Marta M. Ybarra, Catalina Morales-Betancourt, Peter Korcek, Marta Teresa-Palacio, Fabio Mosca, Anja Hergenhan, Nilgun Koksal, Konstantia Tsoni, Munaf M. Kadri, Claudia Knoepfli, Elzbieta Rafinska-Wazny, Mustafa S. Akin, Tone Nordvik, Zhang Peng, Sinem G. Kersin, Liesbeth Thewissen, Ana Alarcon, David Healy, Berndt Urlesberger, Muenevver Bas, Jana Baumgartner, Eleni Skylogianni, Veronika Karadyova, Eva Valverde, Elena Bergon-Sendin, Jachym Kucera, Silvia Pisoni, Le Wang, Anne Smits, Rebeca Sanchez-Salmador, Marie I. Rasmussen, Markus H. Olsen, Aksel K. Jensen, Christian Gluud, Janus C. Jakobsen, Gorm Greisen
Summary: A multicenter, randomized trial found that treatment guided by cerebral oximetry monitoring for the first 72 hours after birth did not reduce the risk of death or severe brain injury at 36 weeks' postmenstrual age in extremely preterm infants.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Pediatrics
Pieter Schellekens, Marcelien Verjans, Peter Janssens, Angelique Dachy, Stephanie De Rechter, Luc Breysem, Karel Allegaert, Bert Bammens, Rudi Vennekens, Pieter Vermeersch, Hans Pottel, Djalila Mekahli
Summary: This study examined a cohort of 68 genotyped ADPKD patients and compared several commonly used equations for estimating eGFR. The CKiD and CKiDU25 equations showed age or sex differences, while the FAS equations were independent of age and sex. Therefore, having reliable methods to calculate eGFR is crucial for clinical follow-up and trials.
PEDIATRIC NEPHROLOGY
(2023)
Article
Pediatrics
Judith A. ten Barge, Gerbrich E. van den Bosch, Naomi J. Meesters, Karel Allegaert, Cristina Arribas, Giacomo Cavallaro, Felipe Garrido, Genny Raffaeli, Marijn J. Vermeulen, Sinno H. P. Simons
Summary: This study aimed to describe the current pain management practices for necrotizing enterocolitis (NEC) patients in European neonatal intensive care units (NICUs). An online survey found that out of the 259 participating units, 61% had a standard analgesic therapy protocol, 73% assessed pain in NEC patients, and 92% treated NEC patients with intravenous analgosedatives. However, there was significant heterogeneity in the pain assessment tools used and the initial analgesic therapy.
PEDIATRIC RESEARCH
(2023)
Article
Public, Environmental & Occupational Health
Jill Vanthienen, Marine Vassilev Petrov, Thuy Mai Luu, Anik Cloutier, Anke Raaijmakers, Jan A. Staessen, Zhenyu Zhang, Thomas Salaets, Annouschka Laenen, Anne Smits, Anne-Monique Nuyt, Adrien Flahault, Karel Allegaert
Summary: The study found no significant difference in QT(c-Bazett) intervals between former preterm and/or extremely low birth weight cases and term-born controls.
Review
Biochemistry & Molecular Biology
Karen Leys, Marina-Stefania Stroe, Pieter Annaert, Steven Van Cruchten, Sebastien Carpentier, Karel Allegaert, Anne Smits
Summary: Perinatal asphyxia (PA) continues to have significant morbidity and mortality rates. Therapeutic hypothermia (TH) is the only effective treatment for neonates with moderate to severe hypoxic-ischemic encephalopathy after PA. Additional pharmacotherapy may be necessary for these neonates, and both PA and TH can affect physiology and, consequently, pharmacokinetics (PK) and pharmacodynamics (PD).
EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY
(2023)
Article
Pediatrics
Liam Mahoney, Genny Raffaeli, Serdar Beken, Sezin Unal, Charalampos Kotidis, Giacomo Cavallaro, Felipe Garrido, Aomesh Bhatt, Eugene M. Dempsey, Karel Allegaert, Sinno H. P. Simons, Robert B. Flint, Anne Smits, ESPR Pharmacology Sect
Summary: There is a reasonable level of evidence for the pharmacotherapy of midazolam and phenobarbital in neonates. However, most of the evidence is based on pharmacokinetic studies without integrated pharmacodynamic evaluation. Further research is needed on the use of midazolam in term neonates with therapeutic hypothermia and phenobarbital treatment in preterm neonates.
PEDIATRIC RESEARCH
(2023)
Article
Pediatrics
Caroline di Gangi, Maren Hermans, Maissa Rayyan, Francois Eyskens, Karel Allegaert
Summary: A pilot study was conducted to assess mothers' knowledge of newborn bloodspot screening (NBS), including the procedure and information sources. The study found that mothers had a good understanding of screening concepts and the absence of notification regarding normal findings. However, their knowledge of NBS not being compulsory and post-analysis sample handling procedures was limited. Key healthcare providers were midwives and nurses, and the provision of leaflets supported knowledge transfer. These findings can be used to improve the quality of NBS programs in Flanders.
Review
Obstetrics & Gynecology
Themistoklis Dagklis, Ranjit Akolekar, Cecilia Villalain, Ioannis Tsakiridis, Assaad Kesrouani, Aydin Tekay, Walter Plasencia, Sven Wellmann, Satoshi Kusuda, Nelly Jekova, Federico Prefumo, Nicola Volpe, Petya Chaveeva, Karel Allegaert, Asma Khalil, Cihat Sen
Summary: This practice guideline aims to improve the management of preterm labor and provides further guidance for healthcare practitioners on diagnosing preterm labor and the appropriate use of medications.
EUROPEAN JOURNAL OF OBSTETRICS & GYNECOLOGY AND REPRODUCTIVE BIOLOGY
(2023)
Article
Peripheral Vascular Disease
Yu-Ling Yu, De-Wei An, Wen-Yi Yang, Peter Verhamme, Karel Allegaert, Tim S. Nawrot, Jan A. Staessen
Summary: The Study for Promotion of Health in Recycling Lead (SPHERL) assessed the blood pressure and renal function responses in workers without previous occupational lead exposure over a period of 6 years. The results showed that there was no significant correlation between the changes in blood pressure and renal function and the increase in blood lead level. Therefore, it can be concluded that modern lead-handling facilities operating under current safety rules are safe.
JOURNAL OF CLINICAL HYPERTENSION
(2023)
Letter
Infectious Diseases
Greet Van De Sijpe, Marnix Mylemans, Laura Armengol Alvarez, Agustos Cetin Ozbey, Karel Allegaert, Jef Rozenski, Pieter Annaert, Stefanie Desmet, Isabel Spriet
CLINICAL MICROBIOLOGY AND INFECTION
(2023)
Article
Clinical Neurology
Karlijn Bouman, Jeroen L. M. van Doorn, Jan T. Groothuis, Peter J. Wijkstra, Baziel G. M. van Engelen, Corrie E. Erasmus, Jonne Doorduin, Nicol C. Voermans
Summary: The majority of LAMA2-MD and all SELENON-RM patients had respiratory impairment. SELENON-RM patients showed lower respiratory function which was progressive, more prevalent mechanical ventilation, and more severe diaphragm atrophy and dysfunction than LAMA2-MD patients. Spirometry (FVC%, dVC) and respiratory muscle strength tests (SNIP) are useful in clinical care and as outcome measure in clinical trials.
EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY
(2024)
Article
Clinical Neurology
Oliviero Bruni, Maria Breda, Emanuela Malorgio, Paolo Brambilla, Flavia Ceschin, Andrea Di Pilla, Maurizio Elia, Raffaele Ferri
Summary: This study aimed to describe the use of melatonin by Italian pediatricians in healthy children with chronic insomnia. The results showed that a high percentage of pediatricians prescribed melatonin, especially in children aged 1-2 years. The most common dosage was 1 mg/day and it was usually recommended to be taken 30 minutes before bedtime. Melatonin was often combined with sleep hygiene and was found to be effective in reducing difficulties falling asleep.
EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY
(2024)
Article
Clinical Neurology
Lucie Sedlackova, Katalin Sterbova, Marketa Vlckova, Pavel Seeman, Jana Zarubova, Petr Marusic, Pavel Krsek, Hana Krijtova, Alena Musilova, Petra Lassuthova
Summary: In this study, whole exome sequencing (WES) was performed to identify causal variants for developmental and epileptic encephalopathies (DEEs) in patients whose genetic diagnosis was not determined by gene panel testing. The results showed that WES can successfully identify disease-causing variants, even after inconclusive gene panel testing. Detailed clinical evaluations and phenotype-genotype correlation studies were conducted to better understand the rare subtypes of DEEs.
EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY
(2024)
