Paracetamol Concentrations and Time-Course of Ductus Arteriosus Diameter in Extremely Preterm Neonates: A Population Pharmacokinetic-Pharmacodynamic Analysis.

Background: Patent ductus arteriosus is a common complication of extreme prematurity. Prophylactic treatment with indomethacin or ibuprofen has shown efficacy on ductus closure but without reducing mortality and morbidity. Prophylactic treatment by paracetamol could be a safer alternative.

Ceftazidime-Avibactam Pharmacokinetic Comparative In Vivo/In Vitro Study in a Critically Ill Children Under High-Volume Continuous Venovenous Hemodiafiltration.

Ceftazidime-avibactam is a novel cephalosporin/beta-lactamase inhibitor combination developed to address increasing antimicrobial resistance. This report presents a comparative study of the pharmacokinetics of ceftazidime and avibactam, utilizing in vitro data derived from two experiments with continuous venovenous hemodiafiltration (CVVHDF) simulation and a comparison with a previously published in vivo case report. The results highlight the importance of therapeutic drug monitoring and the need for higher dosing or continuous infusion of ceftazidime-avibactam in critically ill children under crontinuous renal replacement therapy (CRRT).

Comparison of human transplacental transfer of escitalopram, sertraline and paroxetine: an ex vivo cotyledon perfusion study.

Introduction: Depression is common in pregnant women and the decision to treat must consider potential risk to the fetus. Since data on the transplacental transfer of serotonin reuptake inhibitors (SSRIs) remain sparse, we aimed to characterize and compare the transplacental transfer of three commonly used SSRIs in pregnant women: escitalopram, sertraline and paroxetine.

Methods: Ex vivo human placental perfusions in dual recirculating configuration were performed for these three antidepressants with and without albumin over 3 h of perfusion.

Population pharmacokinetic modelling of prednisolone in systemic lupus erythematosus patients: Analysis of exposure and disease activity.

Aims: Prednisone is a widely used glucocorticoid in the treatment of lupus, although its dosing is often determined empirically. Prednisolone, the active metabolite of prednisone, is found in its free form in the serum. The goal of this study was to develop a population pharmacokinetic model in patients with systemic lupus erythematosus (SLE) to forecast free prednisolone concentrations and its association with disease activity.

Population Pharmacokinetics of Elexacaftor, Tezacaftor and Ivacaftor in a Real-World Cohort of Adults with Cystic Fibrosis.

Background And Objectives: Elexacaftor-tezacaftor-ivacaftor (ETI), a combination of cystic fibrosis transmembrane conductance regulator (CFTR) modulators, has become the therapeutic standard of care for most people with cystic fibrosis (pwCF). People with cystic fibrosis exhibit differences in CFTR genotypes and have important differences in phenotypic characteristics including age, body weight, pancreatic status, disease severity, and comorbidities. While these differences predict large interindividual variability (IIV) in ETI exposure, there is a unique dose regimen recommended for adults.

Elexacaftor/Tezacaftor/Ivacaftor Population Pharmacokinetics in Pediatric Patients With Cystic Fibrosis.

Elexacaftor/tezacaftor/ivacaftor (ETI) significantly improves treatment outcomes for people with cystic fibrosis (pwCF) with at least one F508del allele. In 2023, the Food and Drug Administration approved ETI for children with CF aged 2-5 years. However, real-world pharmacokinetic-pharmacodynamic data for ETI in pediatric and adult populations are still limited.

Quantification of maternal and fetal valaciclovir exposure in a pharmacokinetic study of cytomegalovirus-infected pregnant women treated to prevent vertical transmission.

Background: In cases of maternal primary infection with cytomegalovirus (CMV-MPI) maternal treatment with oral valaciclovir 8 g/day has been shown to reduce the risk of fetal infection. The pharmacological profile of this high dosage during pregnancy is not yet known.

Objectives: To quantify maternal-fetal exposure to valaciclovir 8 g/day in a population pharmacokinetic (popPK) study.

Impact of pediatric continuous renal replacement therapy parameters on meropenem, piperacillin, and tazobactam pharmacokinetics: an model.

Background: Limited data exist on how continuous renal replacement therapy (CRRT) affects antimicrobial dosing in pediatric patients. This study examined the impact of pediatric CRRT parameters on the pharmacokinetics (PK) of meropenem, piperacillin, and tazobactam using an in vitro CRRT model.

Research Design And Methods: An in vitro CRRT model with a pediatric ST60 circuit was used to assess antimicrobial clearance during continuous veno-venous hemodialysis (CVVHD) or hemofiltration (CVVH).

A rapid LC-MS/MS method for the simultaneous quantification of ivacaftor, lumacaftor, elexacaftor, tezacaftor, hexyl-methyl ivacaftor and ivacaftor carboxylate in human plasma.

Cystic fibrosis is one of the most common genetic diseases among caucasian population. This disease is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene encoding for the CFTR protein. Lumacaftor, elexacaftor, tezacaftor, and ivacaftor were currently used as the treatment to Cystic fibrosis.

Prophylactic Intravenous Acetaminophen in Extremely Premature Infants: Minimum Effective Dose Research by Bayesian Approach.

Background: Patent ductus arteriosus (PDA) in preterm infants is associated with increased morbidities and mortality. Prophylactic treatment with cyclooxygenase inhibitors, as indomethacin or ibuprofen, failed to demonstrate significant clinical benefits. Acetaminophen may represent an alternative treatment option.

Prednisolone pharmacokinetics after oral prednisone administration in paediatric patients with kidney transplant.

Aims: Glucocorticoids are 1 of the primary treatments in paediatric kidney transplantation. The aims of this study were: (i) to build a population pharmacokinetics (PPK) model of free prednisolone, which is the active form of prednisone, in paediatric kidney transplant recipients; (ii) to identify covariates accounting for interindividual variability (IIV) of pharmacokinetics (PK) parameters; and (iii) to investigate drug exposure-safety relationships.

Methods: Ninety-seven samples were obtained from 39 paediatric kidney transplant recipients (aged 3.

Predictive Performance of Population Pharmacokinetic Models of Levetiracetam in Children and Evaluation of Dosing Regimen.

Levetiracetam is a broad-spectrum antiepileptic drug that exhibits high interindividual variability in serum concentrations in children. A population pharmacokinetic approach can be used to explain this variability and optimize dosing schemes. The objectives are to identify the best predictive population pharmacokinetic model for children and to evaluate recommended doses using simulations and Bayesian forecasting.

Development of a simple and rapid method to determine the unbound fraction of dolutegravir, raltegravir and darunavir in human plasma using ultrafiltration and LC-MS/MS.

Dolutegravir, raltegravir and darunavir are three antiretroviral drugs widely used in combined antiretroviral therapies. These three drugs are highly bound to plasma proteins. Compared to the total concentration, the concentration of unbound drug which is considered as the only pharmacological active form should be more informative to improve therapeutic drug monitoring in patients to avoid virological failure or toxicity.

Maternal Betamethasone for Prevention of Respiratory Distress Syndrome in Neonates: Population Pharmacokinetic and Pharmacodynamic Approach.

Despite antenatal corticosteroids therapy, respiratory distress syndrome (RDS) is still a leading cause of neonatal morbidity and mortality in premature newborns. To date, the relationship between in utero fetal drug exposure and occurrence of RDS remains poorly evaluated. This study aims to describe the pharmacokinetics of betamethasone in pregnant women and to evaluate the transplacental drug transfer and administration scheme for the prevention of RDS.

HPLC-MS/MS method for the simultaneous quantification of dolutegravir, elvitegravir, rilpivirine, darunavir, ritonavir, raltegravir and raltegravir-β-d-glucuronide in human plasma.

Therapeutic drug monitoring (TDM) is essential in the optimization of antiretroviral (ARV) treatments. In this work, we describe a new method for the simultaneous quantification of six molecules: the three novel ARV agents dolutegravir (DTG), elvitegravir (ELV) and rilpivirine (RPV), the first integrase inhibitor raltegravir (RAL) and its major metabolite the raltegravir-β-d-glucuronide (RAL-GLU), an protease inhibitor darunavir (DRV) and its booster ritonavir (RTV) in human plasma. The drugs were extracted from 100 μL of plasma by a simple method of protein precipitation using acetonitrile.

Free prednisolone pharmacokinetics predicted from total concentrations in patients with inflammatory - immunonologic conditions.

Prednisone is an anti-inflammatory drug widely used in internal medicine and rheumatology, but dosing remains empirical. The active metabolite of prednisone is free prednisolone. The aim of this work was to build a population pharmacokinetic (PK) model that can predict free prednisolone concentrations in patients with inflammatory/immunologic conditions.

Methodological Approaches to Evaluate Fetal Drug Exposure.

Background: Drug prescriptions are usual during pregnancy, however, women and their fetuses still remain an orphan population with regard to drugs efficacy and safety. Most xenobiotics diffuse through the placenta and some of them can alter fetus development resulting in structural abnormalities, growth or functional deficiencies.

Methods: To summarize the different methodologies developed towards the prediction of fetal drug exposure.

Simultaneous quantification of levofloxacin, pefloxacin, ciprofloxacin and moxifloxacin in microvolumes of human plasma using high-performance liquid chromatography with ultraviolet detection.

Levofloxacin, pefloxacin, ciprofloxacin and moxifloxacin are four fluoroquinolones used in the treatment of serious bacterial infections. The antibacterial activity of fluoroquinolones is concentration dependent. Therefore, therapeutic drug monitoring in daily clinical practice is warranted to ensure the therapy's efficacy and prevent bacterial resistance.

A Pharmacokinetic and Pharmacogenetic Analysis of Osteosarcoma Patients Treated With High-Dose Methotrexate: Data From the OS2006/Sarcoma-09 Trial.

Growing evidence suggests that polymorphisms of genes coding for transporters or enzymes may partially explain the large between subject variability reported for methotrexate (MTX) pharmacokinetics (PK). This prospective study aimed to develop a population PK-pharmacogenetic model to evaluate the part of between-subject variability due to single-nucleotide polymorphisms (SNPs) in transporters and enzyme genes implicated in MTX distribution and elimination. MTX concentrations and 54 SNPs (located in ABCB1, ABCC1, ABCC2, ABCC3, ABCC4, ABCG2, SLC19A1, SLCO1B1, and UGT1A1 genes) were analyzed in patients treated with MTX included in the OS2006/sarcoma-09 trial (a multicenter, open-label, phase III trial, ClinicalTrials.

Suboptimal cotrimoxazole prophylactic concentrations in HIV-infected children according to the WHO guidelines.

Aims: A clinical study was conduct in HIV-infected children to evaluate the prophylactic doses of cotrimoxazole [sulfamethoxazole (SMX) and trimethoprim (TMP)] advised by the WHO.

Methods: Children received lopinavir-based antiretroviral therapy with cotrimoxazole prophylaxis (200 mg of SMX/40 mg of TMP once daily). A nonlinear mixed effects modelling approach was used to analyse plasma concentrations.