Is the GFR-based scaling approach adequate for predicting pediatric renal clearance of drugs with passive tubular reabsorption? Insights from PBPK modeling.

Empirical maturation models (e.g., Johnson and Rhodin models) for glomerular filtration rate (GFR) are commonly used as scaling factors for predicting pediatric renal clearance, but their predictive performance for drugs featured with tubular reabsorption is poorly understood.

Sample Size Determination and Study Design Impact on Dose-Scale Pharmacodynamic Bioequivalence: a Case Study Using Orlistat.

Dose-scale pharmacodynamic bioequivalence is recommended for evaluating the consistency of generic and innovator formulations of certain locally acting drugs, such as orlistat. This study aimed to investigate the standard methodology for sample size determination and the impact of study design on dose-scale pharmacodynamic bioequivalence using orlistat as the model drug. A population pharmacodynamic model of orlistat was developed using NONMEM 7.

Physiologically based pharmacokinetic modelling of cefoperazone in paediatrics.

Aims: Cefoperazone is commonly used off-label in the treatment of bacterial meningitis and sepsis in children, and the pharmacokinetic (PK) data are limited in this vulnerable population. The goal of this study was to develop a physiologically based pharmacokinetic (PBPK) model to predict pediatric cefoperazone exposure for rational dosing recommendations.

Methods: A cefoperazone PBPK model for adults was first constructed using Simcyp V22 simulator.

Evaluation of Various Approaches to Estimate Transplacental Clearance of Vancomycin for Predicting Fetal Concentrations using a Maternal-Fetal Physiologically Based Pharmacokinetic Model.

Background: Evaluating drug transplacental clearance is vital for forecasting fetal drug exposure. Ex vivo human placenta perfusion experiments are the most suitable approach for this assessment. Various in silico methods are also proposed.

Nonlinear Pharmacokinetics of Topical Flurbiprofen Gel in a Phase I Study Among Chinese Healthy Adults.

Introduction: PDX-02 (Flurbiprofen sodium) is a topical nonsteroidal anti-inflammatory drug in gel formulation for local analgesia and anti-inflammation. A Phase I clinical trial was conducted to assess the safety, tolerability, and pharmacokinetics of single and multiple doses of PDX-02 gel in Chinese healthy adults.

Methods: The trial comprised three parts: (1) a single-dose ascending study with three dose levels (0.

Quantification of oxaliplatin- and ioversol-related compounds in pharmaceutical formulations using novel HPLC-ICP-MS methods.

Purpose: Accurate quantifying of drug-related compounds in medicines is vital for safety. Commonly used structure-dependent methods rely on analytical standards. High-performance liquid chromatography coupled with inductively coupled plasma-mass spectrometry (HPLC-ICP-MS) offers a promising solution, being structure-independent and not requiring standards.

Simulated drug disposition in critically ill patients to evaluate effective PK/PD targets for combating resistance to meropenem.

Bacterial infections, including those caused by , often lead to sepsis, necessitating effective antibiotic treatment like carbapenems. The key pharmacokinetic/pharmacodynamic (PK/PD) index correlated to carbapenem efficacy is the fraction time of unbound plasma concentration above the minimum inhibitory concentration (MIC) of the pathogen (% > MIC). While multiple targets exist, determining the most effective one for critically ill patients remains a matter of debate.

Development and validation of a UPLC-PDA method for quantifying ceftazidime in dried blood spots.

Bacterial infection is a leading cause of neonatal death. Ceftazidime, commonly used for neonatal infections, is often used off-label. Blood sampling limits pharmacokinetic (PK) studies in neonatal patients.

Multistate modeling for survival analysis in critically ill patients treated with meropenem.

Appropriate antibiotic dosing to ensure early and sufficient target attainment is crucial for improving clinical outcome in critically ill patients. Parametric survival analysis is a preferred modeling method to quantify time-varying antibiotic exposure - response effects, whereas bias may be introduced in hazard functions and survival functions when competing events occur. This study investigated predictors of in-hospital mortality in critically ill patients treated with meropenem by pharmacometric multistate modeling.

Linezolid dosing in critically ill patients undergoing various modalities of renal replacement therapy: a pooled population pharmacokinetic analysis.

The altered pharmacokinetics (PK) of linezolid are pronounced in critically ill patients undergoing different modalities of renal replacement therapy (RRT). This study aimed to provide a pooled population PK analysis of linezolid in patients undergoing RRT, and to evaluate the pharmacodynamic target attainment of linezolid standard dosing (600 mg q12h). In total, 414 pooled linezolid concentration observations from 69 patients undergoing intermittent haemodialysis (IHD), sustained low-efficiency dialysis (SLED) or continuous RRT were used to develop the population PK model.

Review on Wood Deformation and Cracking during Moisture Loss.

Wood, being a natural hygroscopic material, the interaction between wood and moisture plays a crucial role in wood processing and utilization. Moisture affects the physical and mechanical properties of wood, and is also one of the main external factors that cause wood deformation and cracking. Drying shrinkage is a common phenomenon during the processing and utilization of wood induced by moisture loss.

A semimechanistic pharmacokinetic/pharmacodynamic model for alanine aminotransferase-based hepatotoxicity of methotrexate in paediatric patients with acute lymphoid leukaemia.

Aims: Methotrexate (MTX) is recognized for its potential to induce hepatotoxicity, commonly manifested by elevated alanine aminotransferase (ALT) levels. However, the quantitative relationship between the pharmacokinetics (PK) of MTX and ALT-based hepatotoxicity remains unclear. This study aimed to develop a semimechanistic PK/pharmacodynamic (PD) model to characterize the MTX-induced hepatotoxicity based on ALT in paediatric patients with acute lymphoid leukaemia.

Development of polyanion-metal ion solution systems to overcome phospholipids-related matrix effects in LC-MS/MS-based bioanalysis.

Phospholipids-related matrix effects are a major source impacting the reproducibility of analyte quantification in LC-MS/MS-based bioanalysis. This study intended to evaluate different combinations of polyanion-metal ion based solution system for phospholipids removal and elimination of matrix effects in human plasma. Blank plasma samples or plasma samples spiked with model analytes were proceeded with different combinations of polyanions (dextran sulfate sodium (DSS) and alkalized colloidal silica (Ludox)) and metal ions (MnCl, LaCl, and ZrOCl) followed with acetonitrile-based protein precipitation.

Population pharmacokinetic/pharmacodynamic evaluations of amikacin dosing in critically ill patients undergoing continuous venovenous hemodiafiltration.

Objectives: The pharmacokinetics/pharmacodynamics (PK/PD) of amikacin in critically ill patients undergoing continuous venovenous hemodiafiltration (CVVHDF) are poorly described, and appropriate dosing is unclear in this patient population. This study aimed to develop a population PK model of amikacin and to provide systemic PK/PD evaluations for different dosing regimens in CVVHDF patients.

Methods: One hundred and sixty-one amikacin concentration observations from thirty-three CVVHDF patients were pooled to develop the population PK model.

External Evaluation of Population Pharmacokinetic Models of Methotrexate for Model-Informed Precision Dosing in Pediatric Patients with Acute Lymphoid Leukemia.

Background: Methotrexate (MTX) is a key immunosuppressant for children with acute lymphoid leukemia (ALL), and it has a narrow therapeutic window and relatively high pharmacokinetic variability. Several population pharmacokinetic (PopPK) models of MTX in ALL children have been reported, but the validity of these models for model-informed precision dosing in clinical practice is unclear. This study set out to evaluate the predictive performance of published pediatric PopPK models of MTX using an independent patient cohort.

A Validated UHPLC-MS/MS Method to Quantify Eight Antibiotics in Quantitative Dried Blood Spots in Support of Pharmacokinetic Studies in Neonates.

Objectives: Conduction of pharmacokinetic (PK) study in pediatric patients is challenging due to blood sampling limits. The dried blood spots (DBS) method represents a potential matrix for microsampling in support of PK studies in children. Herein, we used the Capitainer qDBS device to develop a DBS method that can collect an exact 10 µL volume of blood on a paper card.

Defining Exposure Predictors of Meropenem That Are Associated with Improved Survival for Severe Bacterial Infection: A Preclinical PK/PD Study in Sepsis Rat Model.

Background: The pharmacokinetic/pharmacodynamic (PK/PD) index of carbapenems that best correlates with in vivo antimicrobial activity is percent time of dosing interval in which free drug concentration remains above MIC (%fT > MIC), while the magnitudes of the PK/PD index of carbapenems remains undefined in critically ill sepsis patients. Methods: A sepsis rat model was first developed by comparing the survival outcomes after intraperitoneal injection of different inoculum size (1−10 × 107 CFU) of Pseudomonas aeruginosa ATCC9027 (MIC = 0.125 mg/L) in neutropenic rats.

Foetal and neonatal exposure prediction and dosing evaluation for ampicillin using a physiologically-based pharmacokinetic modelling approach.

Aims: Ampicillin is frequently used in neonates for the treatment of sepsis and as an intrapartum prophylaxis option for Group B Streptococcus. Pharmacokinetic data to guide ampicillin dosing in neonates and during the intrapartum period are limited. The objective of this study was to build a physiologically-based pharmacokinetic (PBPK) model to characterize the disposition of ampicillin in neonates and foetuses and to inform corresponding optimal dosing regimens.

Population Pharmacokinetic Meta-Analysis and Dosing Recommendation for Meropenem in Critically Ill Patients Receiving Continuous Renal Replacement Therapy.

The optimal dosing regimen for meropenem in critically ill patients undergoing continuous renal replacement therapy (CRRT) remains undefined due to small studied sample sizes and uninformative pharmacokinetic (PK)/pharmacodynamic (PD) analyses in reported studies. The present study aimed to perform a population PK/PD meta-analysis of meropenem using available literature data to suggest the optimal treatment regimen. A total of 501 meropenem concentration measurements from 78 adult CRRT patients pooled from nine published studies were used to develop the population PK model for meropenem.

Structural Properties and Hydrolysability of : The Effects of Pretreatment Methods Based on Acetic Acid and Its Combination with Sodium Sulfite or Sodium Sulfite.

The effects of CHCOOH and NaSO pretreatment on the structural properties and hydrolyzability of fast-growing were investigated. Acetic acid increased cellulose's crystallinity and hydrolyzability when combined with alkaline sodium sulfite and sodium hydroxide. The cellulose content increased by 21%, the lignin content decreased by 6%, and the product showed better enzymatic digestibility.

Pharmacokinetic/pharmacodynamic-guided gentamicin dosing in critically ill patients: a revisit of the Hartford nomogram.

The appropriateness of the Hartford nomogram based on 7 mg/kg gentamicin with administration interval adjustment is questioned in critically ill patients. This study aimed to perform a pharmacokinetic/pharmacodynamic (PK/PD) evaluation of the Hartford nomogram and to assess the influence of PK/PD indices on gentamicin dosing. Gentamicin data were extracted from a critical care database to construct the population PK model.

Population Pharmacokinetics and Dosing Optimization of Gentamicin in Critically Ill Patients Undergoing Continuous Renal Replacement Therapy.

Purpose: Appropriate gentamicin dosing in continuous renal replacement therapy (CRRT) patients remains undefined. This study aimed to develop a population pharmacokinetic (PK) model of gentamicin in CRRT patients and to infer the optimal dosing regimen for gentamicin.

Methods: Fourteen CRRT patients dosed with gentamicin were included to establish a population PK model to characterize the variabilities and influential covariates of gentamicin.

An UPLC-PDA assay for simultaneous determination of seven antibiotics in human plasma.

Appropriate antibiotic dosing in critically ill patients requires concentration monitoring due to the occurrence of pathophysiological changes and frequent extracorporeal therapy that could significantly alter the normal pharmacokinetics of drugs. Herein, we describe an ultra-performance liquid chromatography with photodiode array (UPLC-PDA) for the simultaneous concentration determination of seven frequently used antibiotics (meropenem, cefotaxime, cefoperazone, piperacillin, linezolid, moxifloxacin, and tigecycline) in plasma from critically ill patients. The analytes were extracted from 200 μL human plasma by the addition of methanol for protein precipitation.