: After administration, a drug undergoes absorption, distribution, metabolism, and elimination (ADME) before exerting its effect on the body. The combination of these process yields the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of a drug. Although accurate prediction of PK and PD profiles is essential for drug development, conventional in vitro models are limited by their lack of physiological relevance. Recently, microtechnology-based in vitro model systems, termed 'organ-on-a-chip,' have emerged as a potential solution.: Orally administered drugs are absorbed through the intestinal wall and transported to the liver before entering systemic circulation, which plays an important role in the PK and PD profiles. Recently developed, chip-based in vitro models can be useful models for simulating such processes and will be covered in this paper.: The potential of intestine-on-a-chip models combined with conventional PK-PD modeling has been demonstrated with promising preliminary results. However, there are several challenges to overcome. Development of the intestinal wall, integration of the gut microbiome, and the provision of an intestine-specific environment must be achieved to realize in vivo-like intestinal model and enhance the efficiency of drug development.
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http://dx.doi.org/10.1080/17425255.2019.1700950 | DOI Listing |
J Pediatric Infect Dis Soc
January 2025
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Background: The Infectious Diseases Society of America (IDSA) publishes annual guidance on the treatment of antimicrobial-resistant (AMR) gram-negative infections. Within the AMR guidance, suggested dosages of antibiotics for adults infected with AMR pathogens are provided. This document serves as a companion document to the IDSA guidance to assist pediatric specialists with dosing β-lactam agents for the treatment of AMR infections in children.
View Article and Find Full Text PDFJ Antimicrob Chemother
January 2025
Department of Pharmacy, Uppsala University, Uppsala, Sweden.
Objectives: This study aimed to predict the impact of different infusion strategies on pharmacokinetic/pharmacodynamic (PK/PD) target attainment and the potential risk for toxicity in an ICU cohort treated with β-lactams.
Method: Using collected patient data from 137 adult ICU patients, and applying population PK models, individual PK parameters were estimated and used to predict concentrations and target attainment following cefotaxime 2 g q8h, piperacillin/tazobactam 4.5 g q6h and meropenem 1 g q8h, applying 15 min short infusions (SI), 3 h extended infusions (EI) and 24 h continuous infusion (CI).
Blood Res
January 2025
Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Cancer Research Institute, Seoul, Republic of Korea.
Purpose: This study compared the outcomes of haploidentical-related donor (HRD) and umbilical cord blood (UCB) hematopoietic stem cell transplantation (HSCT) in pediatric patients with hematologic malignancies.
Methods: Data on patients who underwent HRD HSCT with post-transplant cyclophosphamide (n = 41) and UCB HSCT (n = 24) after targeted busulfan-based myeloablative conditioning with intensive pharmacokinetic monitoring between 2009 and 2018 were retrospectively analyzed.
Results: The median follow-up durations in the HRD and UCB groups were 7.
Ther Drug Monit
January 2025
Children's Hospital Los Angeles, Los Angeles, California; and.
Background: Area-under-the-curve (AUC)-directed vancomycin therapy is recommended; however, AUC estimation in critically ill children is difficult owing to the need for multiple samples and lack of informative models.
Methods: The authors prospectively enrolled critically ill children receiving intravenous (IV) vancomycin for suspected infection and evaluated the accuracy of Bayesian estimation of AUC from a single, optimally timed sample. During the dosing interval, when clinical therapeutic drug monitoring was performed, an optimally timed sample was collected, which was determined for each subject using an established population pharmacokinetic model and the multiple model optimal function of Pmetrics, a nonparametric population pharmacokinetic modeling software.
Pediatr Rep
January 2025
Department of Pharmacology and Toxicology, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34 000 Kragujevac, Serbia.
The aim of our study was to investigate the role of polymorphism in the pharmacokinetics of carbamazepine (CBZ) in children. The study enrolled 47 Serbian pediatric epileptic patients on CBZ treatment. Genotyping for 1236C
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