Simultaneous determination of the combined and free concentrations of atorvastatin and its major metabolite and based on ultrafiltration coupled with UPLC-MS/MS method: an application in a protein binding rate and metabolism ability study in uremic hemodialysis patients.

Introduction: A rapid, accurate, and specific ultrafiltration with ultra-performance liquid chromatographic-tandem mass spectrometry method was validated for the simultaneous determination of the protein binding rate of atorvastatin in uremic patients. Methods: The plasma samples were centrifuged at 6,000 r/min for 15 min at 37°C and the ultrafiltrate was collected. An ACQUITY UPLC® BEH C18 Column with gradient elution of water (0.

Machine Learning Approach in Dosage Individualization of Isoniazid for Tuberculosis.

Introduction: Isoniazid is a first-line antituberculosis agent with high variability, which would profit from individualized dosing. Concentrations of isoniazid at 2 h (C), as an indicator of safety and efficacy, are important for optimizing therapy.

Objective: The objective of this study was to establish machine learning (ML) models to predict the C, that can be used for establishing an individualized dosing regimen in clinical practice.

Optimal use of β-lactams in neonates: machine learning-based clinical decision support system.

Background: Accurate prediction of the optimal dose for β-lactam antibiotics in neonatal sepsis is challenging. We aimed to evaluate whether a reliable clinical decision support system (CDSS) based on machine learning (ML) can assist clinicians in making optimal dose selections.

Methods: Five β-lactam antibiotics (amoxicillin, ceftazidime, cefotaxime, meropenem and latamoxef), commonly used to treat neonatal sepsis, were selected.

Efficacy, Safety, and Population Pharmacokinetics of Eltrombopag in Children with Different Severities of Aplastic Anemia.

Eltrombopag was approved as a first-line treatment for patients older than 2 years old with severe aplastic anemia (SAA). However, data on eltrombopag in children with different types of aplastic anemia (AA), especially non-severe AA (NSAA), are limited. We performed a prospective, single-arm, and observational study to investigate eltrombopag's efficacy, safety, and pharmacokinetics in children with NSAA, SAA, and very severe AA (VSAA).

A first-in-human phase 1 study of simnotrelvir, a 3CL-like protease inhibitor for treatment of COVID-19, in healthy adult subjects.

Safe and efficacious antiviral therapeutics are in urgent need for the treatment of coronavirus disease 2019. Simnotrelvir is a selective 3C-like protease inhibitor that can effectively inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated the safety, tolerability, and pharmacokinetics of dose escalations of simnotrelvir alone or with ritonavir (simnotrelvir or simnotrelvir/ritonavir) in healthy subjects, as well as the food effect (ClinicalTrials.

Machine Learning: A New Approach for Dose Individualization.

The application of machine learning (ML) has shown promising results in precision medicine due to its exceptional performance in dealing with complex multidimensional data. However, using ML for individualized dosing of medicines is still in its early stage, meriting further exploration. A systematic review of study designs and modeling details of using ML for individualized dosing of different drugs was performed.

Use of Machine Learning for Dosage Individualization of Vancomycin in Neonates.

Background And Objective: High variability in vancomycin exposure in neonates requires advanced individualized dosing regimens. Achieving steady-state trough concentration (C) and steady-state area-under-curve (AUC) targets is important to optimize treatment. The objective was to evaluate whether machine learning (ML) can be used to predict these treatment targets to calculate optimal individual dosing regimens under intermittent administration conditions.

Developmental Population Pharmacokinetics-Pharmacodynamics of Meropenem in Chinese Neonates and Young Infants: Dosing Recommendations for Late-Onset Sepsis.

The pharmacokinetic (PK) studies of meropenem in Chinese newborns with late-onset sepsis (LOS) are still lacking. Causative pathogens of LOS and their susceptibility patterns in China differ from the data abroad. We, therefore, conducted a developmental population pharmacokinetic−pharmacodynamic analysis in Chinese newborns with the goal to optimize meropenem dosing regimens for LOS therapy.

Fabrication of anti-icing/de-icing surfaces by femtosecond laser.

In this minireview, we comprehensively reviewed recent progress on fabricating anti-icing/de-icing surfaces by femtosecond laser technologies. Typical bioinspired micro-/nano-structures fabrication strategies, superhydrophobic surfaces with anti-icing properties, and photothermal surfaces with de-icing properties are summarized. At last, we discussed challenges and prospects in anti-icing/de-icing surfaces fabricated by femtosecond laser technologies.

Meropenem for children with severe pneumonia: Protocol for a randomized controlled trial.

Pneumonia, caused by infection or other factors, seriously endangers the health of children. Meropenem is an effective broad-spectrum antibiotic using in the treatment of infectious diseases. In the therapy of pneumonia, meropenem is mostly employed for the treatment of moderate to severe pneumonia.

Epithelial lining fluid concentrations of ceftriaxone in children with community-acquired pneumonia.

Ceftriaxone is widely used in children with community-acquired pneumonia. Currently, there are no available data regarding epithelial lining fluid (ELF) concentrations of ceftriaxone in children. Thus, blood and bronchoalveolar lavage fluids samples were collected by using an opportunistic sampling design, then we determined plasma and ELF concentrations in 22 children (0.

Clinical utility of a model-based amoxicillin dosage regimen in neonates with early-onset sepsis.

Early-onset sepsis (EOS) is one of the most significant causes of morbidity and mortality in neonates. Currently, amoxicillin is empirically used to treat neonates with EOS. However, data on its effectiveness in neonates with EOS are still limited.

Population pharmacokinetics and dosing optimization of mezlocillin in neonates and young infants.

Objectives: Mezlocillin is used in the treatment of neonatal infectious diseases. However, due to the absence of population pharmacokinetic studies in neonates and young infants, dosing regimens differ considerably in clinical practice. Hence, this study aimed to describe the pharmacokinetic characteristics of mezlocillin in neonates and young infants, and propose the optimal dosing regimen based on the population pharmacokinetic model of mezlocillin.

Predictive Performance of Pharmacokinetic Model-Based Virtual Trials of Vancomycin in Neonates: Mathematics Matches Clinical Observation.

Background And Objective: Vancomycin is frequently used to treat Gram-positive bacterial infections in neonates. However, there is still no consensus on the optimal initial dosing regimen. This study aimed to assess the performance of pharmacokinetic model-based virtual trials to predict the dose-exposure relationship of vancomycin in neonates.

Effect of drug combination on tacrolimus target dose in renal transplant patients with different genotypes.

Various factors, including genetic polymorphisms, drug-drug interactions, and patient characteristics influence the blood concentrations of tacrolimus in renal transplant patients. In the present study, we established a population pharmacokinetic model to explore the effect of combined use of Wuzhi capsules/echinocandins and the patients' biochemical parameters such as haematocrit on blood concentrations and target doses of tacrolimus in renal transplant patients with different genotypes. The aim of the study was to propose an individualised tacrolimus administration regimen for early renal transplant recipients.

Optimal Sample Size for Use in Neonatal Pharmacokinetic Studies.

Background: In recent years, population pharmacokinetics (PK) has been widely used in neonatal pharmacology. However, the sample size selection for neonatal PK studies has been highly variable and without clear consensus, especially for drugs with large individual variability. Therefore, this study's objective was to investigate the optimal sample size for use in neonatal PK studies.

LPS-Induced Inflammation Affects Midazolam Clearance in Juvenile Mice in an Age-Dependent Manner.

Purpose: Inflammation has a significant impact on CYP3A activity. We hypothesized that this effect might be age dependent. Our objective was to conduct a population pharmacokinetic study of midazolam in mice at different developmental stages with varying degrees of inflammation to verify our hypothesis.

Downregulation of Renal MRPs Transporters in Acute Lymphoblastic Leukemia Mediated by the IL-6/STAT3/PXR Signaling Pathway.

Purpose: Considering prior investigations on reductions of renal multidrug resistance-associated protein (MRP) 2 and 4 transporters in mice with acute lymphoblastic leukemia (ALL), we sought to characterize the underlying mechanisms responsible for IL-6/STAT3/PXR-mediated changes in the expression of MRP2 and MRP4 in ALL.

Subjects And Methods: ALL xenograft models were established and intravenously injected with methotrexate (MTX) of MRPs substrate in NOD/SCID mice. Protein expression of MRPs and associated mechanisms were detected by Western blotting and immunocytochemistry.

Drug Clearance in Neonates: A Combination of Population Pharmacokinetic Modelling and Machine Learning Approaches to Improve Individual Prediction.

Background: Population pharmacokinetic evaluations have been widely used in neonatal pharmacokinetic studies, while machine learning has become a popular approach to solving complex problems in the current era of big data.

Objective: The aim of this proof-of-concept study was to evaluate whether combining population pharmacokinetic and machine learning approaches could provide a more accurate prediction of the clearance of renally eliminated drugs in individual neonates.

Methods: Six drugs that are primarily eliminated by the kidneys were selected (vancomycin, latamoxef, cefepime, azlocillin, ceftazidime, and amoxicillin) as 'proof of concept' compounds.