Pharmacokinetics of oral spironolactone in infants up to 2 years of age.

Purpose: Spironolactone is a potassium sparing diuretic used for decades. Until now, pharmacokinetic (PK) studies of spironolactone have not been conducted in infants and therefore pediatric dosing is based on expert opinion. We aimed to describe the PK profiles of spironolactone and its main metabolites (7alpha-thiomethylspironolactone (TMS) and canrenone (CAN)) in infants up to two years of age.

Availability of Safe and Effective Therapeutic Options to Pregnant and Lactating Individuals Following the United States Food and Drug Administration Pregnancy and Lactation Labeling Rule.

Objective: To explore the extent and type of pregnancy and lactation data of newly approved prescription drugs and assess whether the presented recommendations are data-driven, as required by the US Food and Drug Administration Pregnancy and Lactation Labeling Rule implemented in 2015.

Study Design: In this descriptive analysis, we reviewed pregnancy and lactation data of all new molecular entities approved between 2001 and 2020 in their most updated labeling. Information was collected regarding the pregnancy and lactation risk statements, the source of pregnancy and lactation data, and the design and methods of pregnancy and lactation studies in the labeling.

Efficacy and Safety of NSAIDs in Infants: A Comprehensive Review of the Literature of the Past 20 Years.

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used in infants, children, and adolescents worldwide; however, despite sufficient evidence of the beneficial effects of NSAIDs in children and adolescents, there is a lack of comprehensive data in infants. The present review summarizes the current knowledge on the safety and efficacy of various NSAIDs used in infants for which data are available, and includes ibuprofen, dexibuprofen, ketoprofen, flurbiprofen, naproxen, diclofenac, ketorolac, indomethacin, niflumic acid, meloxicam, celecoxib, parecoxib, rofecoxib, acetylsalicylic acid, and nimesulide. The efficacy of NSAIDs has been documented for a variety of conditions, such as fever and pain.

Personalised therapeutic management of epileptic patients guided by pathway-driven breath metabolomics.

Background: Therapeutic management of epilepsy remains a challenge, since optimal systemic antiseizure medication (ASM) concentrations do not always correlate with improved clinical outcome and minimal side effects. We tested the feasibility of noninvasive real-time breath metabolomics as an extension of traditional therapeutic drug monitoring for patient stratification by simultaneously monitoring drug-related and drug-modulated metabolites.

Methods: This proof-of-principle observational study involved 93 breath measurements of 54 paediatric patients monitored over a period of 2.

Plasma concentration guided dosing of drugs used for the treatment of childhood leukaemias: protocol for a systematic review.

Introduction: Childhood leukaemia is the most common type of cancer in children and represents among 25% of the diagnoses in children <15 years old. Childhood survival rates have significantly improved within the last 40 years due to a rapid advancement in therapeutic interventions. However, in high-risk groups, survival rates remain poor.

A simplified method for bortezomib determination using dried blood spots in combination with liquid chromatography/tandem mass spectrometry.

Bortezomib, a proteinase inhibitor currently used to treat multiple myeloma and mantle cell lymphoma, has a high incidence of adverse reactions and large inter-individual differences in plasma concentrations. A simple, validated LC-MS/MS method for the quantitative analysis of bortezomib in dried blood spot (DBS) samples was developed to provide support for determining the effective concentration range of bortezomib for clinical use. Fifty (i50) μL of spiked blood were added onto Whatman protein saver cards to prepare the DBS samples.

Intrauterine Growth Retardation in Pregnant Women with Long QT Syndrome Treated with Beta-Receptor Blockers.

Pregnant women with inherited long QT syndrome (iLQTS) are at an increased risk for preterm delivery and intrauterine growth retardation (IUGR) due to their underlying disease. Additionally, they are at a risk of arrhythmogenic events, particularly during the postpartum period because of physiological changes and increased emotional/physical stress. β-receptor blockers can effectively prevent life-threatening Torsades de Pointes ventricular tachycardia and they are the treatment of choice in iLQTS.

COVID-19 in Autoinflammatory Diseases with Immunosuppressive Treatment.

COVID-19 disease increases interleukin (IL)-1β release. Anti-IL-1-treatment is effective in IL-1-mediated autoinflammatory diseases (AID). This case series presents COVID-19 in patients with IL-1-mediated and unclassified AID with immunosuppressive therapy (IT).

Pharmacokinetics and safety of pegylated recombinant human granulocyte colony-stimulating factor in children with acute leukaemia.

Aims: This open-label, phase I study evaluated the pharmacokinetics and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) for the treatment of chemotherapy-induced neutropenia in children with acute leukaemia.

Methods: PEG-rhG-CSF was administered as a single 100 mcg/kg (3 mg maximum dose) subcutaneous injection at the end of each chemotherapy period when neutropenia occurred. Blood samples were obtained from patients treated with PEG-rhG-CSF.

Monitoring the recovery time of children after tonsillectomy using commercial activity trackers.

An observational prospective feasibility study in which children received a tracker 2 weeks before a tonsillectomy and were required to wear it until four weeks postoperatively. The parents used a diary to log the estimated steps of their child. As primary endpoint, the compliance of complete datasets was compared between the tracker and the diary.

Randomised placebo-controlled multicentre effectiveness trial of adjunct betamethasone therapy in hospitalised children with community-acquired pneumonia: a trial protocol for the KIDS-STEP trial.

Introduction: Community-acquired pneumonia (CAP) causes around 10 hospitalisations per 1000 child-years, each associated with an average 13 non-routine days experienced and more than 4 parent workdays lost. In adults, steroid treatment shortens time to clinical stabilisation without an increase in complications in patients with CAP. However, despite promising data from observational studies, there is a lack of high-quality evidence for the use of steroids.

Drug-drug and drug-food interactions in an infant with early-onset SCN2A epilepsy treated with carbamazepine, phenytoin and a ketogenic diet.

Sodium channel 2 subunit α (SCN2A) mutations cause difficult-to-treat early-onset epilepsy. Effective treatment includes high-dose phenytoin or carbamazepine ± ketogenic diet (KD). We describe an infant with early-onset SCN2A-epilepsy with subtherapeutic carbamazepine concentration during transition from phenytoin treatment to avoid long-term neurotoxicity.

Implications of Perioperative Polypharmacy in Adolescents Undergoing Bariatric Surgery: a Single-Center Experience.

Adolescents seeking bariatric surgery may present with pre-existing psychiatric diagnoses for which they use chronic medications. To heighten awareness concerning perioperative polypharmacy in adolescents with extreme obesity, we conducted a retrospective review of patients undergoing laparoscopic sleeve gastrectomy between February 2010 and May 2017 at Children's National Health System (CNHS). A total of 167 adolescent patients had pre-existing psychiatric diagnoses which included depression (50%), anxiety (23%), ADHD (23%), and binge eating disorder (11%).

Making Meaningful Improvements in Pharmacotherapy and Medication Management for Children and Youth-A Modest Proposal.

The Special Issue, "Development of a National Pediatric Pharmacotherapy Collaborative Practice Network," has illuminated the vital global need for better care coordination and interprofessional collaboration in pharmacotherapy and medication management of children with medical complexity and special healthcare needs (CSHCN-CMC) [...

Prophylactic Use of Enoxaparin in Adolescents During Bariatric Surgery-a Prospective Clinical Study.

Introduction: Severe obesity predisposes youth to a higher risk of venous thromboembolism (VTE). This study evaluates a BMI-stratified prophylactic dosing regimen of enoxaparin in adolescents with severe obesity undergoing surgery.

Methods: Adolescents aged 12-20 years received prophylactic enoxaparin at 40 mg SC (for a BMI < 50 kg/m) and 60 mg SC (for a BMI ≥ 50 kg/m) every 12 h until discharge.

Dose evaluation of intravenous metamizole (dipyrone) in infants and children: a prospective population pharmacokinetic study.

Purpose: The prodrug metamizole is prescribed intravenously for postoperative pain in children, including off-label use in infants < 1 year. We aimed to assess the pharmacokinetics of the main metabolites of metamizole in children aged 3-72 months.

Methods: A single dose of 10 mg/kg metamizole was administered intravenously for postoperative analgesia.

Population pharmacokinetic meta-analysis of individual data to design the first randomized efficacy trial of vancomycin in neonates and young infants.

Objectives: In the absence of consensus, the present meta-analysis was performed to determine an optimal dosing regimen of vancomycin for neonates.

Methods: A 'meta-model' with 4894 concentrations from 1631 neonates was built using NONMEM, and Monte Carlo simulations were performed to design an optimal intermittent infusion, aiming to reach a target AUC0-24 of 400 mg·h/L at steady-state in at least 80% of neonates.

Results: A two-compartment model best fitted the data.

Creating a Pharmacotherapy Collaborative Practice Network to Manage Medications for Children and Youth: A Population Health Perspective.

Children with special health care needs (CSHCN) use relatively high quantities of healthcare resources and have overall higher morbidity than the general pediatric population. Embedding clinical pharmacists into the Patient-Centered Medical Home (PCMH) to provide comprehensive medication management (CMM) through collaborative practice agreements (CPAs) for children, especially for CSHCN, can improve outcomes, enhance the experience of care for families, and reduce the cost of care. Potential network infrastructures for collaborative practice focused on CSHCN populations, common language and terminology for CMM, and clinical pharmacist workforce estimates are provided.

Toolkit for Population Health Initiatives Around the Globe Related to Collaborative Comprehensive Medication Management for Children and Youth.

Almost 30 million babies worldwide are born prematurely or become ill annually and need specialized care to survive. Formalized collaborative practice agreements (CPA) between clinical pharmacists and physicians have been put forward as a means for improving the overall medicating experience in many patient populations, including children. This report briefly describes opportunities for collaboration using examples from countries on each continent where CPA is established in professional governance documents and standards.

Clinical Pharmacokinetic Studies in Pregnant Women and the Relevance of Pharmacometric Tools.

Background: In clinical pharmacokinetic (PK) studies, pregnant women are significantly underrepresented because of ethical and legal reasons which lead to a paucity of information on potential PK changes in this population. As a consequence, pharmacometric tools became instrumental to explore and quantify the impact of PK changes during pregnancy.

Methods: We explore and discuss the typical characteristics of population PK and physiologically based pharmacokinetic (PBPK) models with a specific focus on pregnancy and postpartum.