Journal of Pediatric Pharmacology and Therapeutics最新文献

Objective: Since 2011, Ampicillin (AMP) has been recommended as the parenteral antibiotic of choice for pediatric community-acquired pneumonia (CAP), but ceftriaxone (CRO) is recommended for unvaccinated children and those with complicated CAP. Using penicillin and CRO susceptibility data for pneumococcus, we evaluated the adequacy of currently recommended doses of AMP and CRO.

Methods: With nonlinear mixed-effects modeling v7.3, Monte Carlo simulations (MCS, N = 10,000) for AMP and CRO were conducted for 6 virtual patients aged 3 months, 1, 2, 5, 10, and 15 years. PK-Sim v9.0 was used to develop physiologic-based pharmacokinetic (PBPK) models for AMP (N = 4000) and CRO (N = 3000). The probability of target attainment (PTA) was determined for both serum and lung (epithelial lining fluid [ELF]) exposure to achieve free drug concentrations above the minimum inhibitory concentration (%fT>MIC) for pneumococci at 30% to 50% of the dosing interval.

Results: We performed simulations based on susceptibility data from 21 pneumococci isolated from children with CAP and found all 21 (100%) to be susceptible to AMP and CRO using Clinical & Laboratory Standard Institute/US Food and Drug Administration breakpoints, where susceptible, intermediate, and resistant strains of Streptococcus pneumoniae were ≤1, 2, and ≥4 mg/L for CRO and ≤2, 4, and ≥8 mg/L for AMP (extrapolated from penicillin), respectively (where intermediate and resistant were considered nonsusceptible); and 18 (85.7%) were susceptible to AMP, and 19 (90.5%) to CRO using the European Committee on Antimicrobial Susceptibility Testing/European Medicines Agency breakpoints, where susceptible and nonsusceptible strains were as follows: 0.5 and 2 mg/L for CRO and 0.5 and 1 mg/L for AMP. Both the serum and ELF, antibiotic regimens achieved >99% PTA at 30% to 50% fT>MIC using MCS and PBPK.

Conclusion: In the pneumococcal conjugate era, standard doses of AMP and CRO appear to provide the appropriate serum and ELF exposure for clinical and microbiologic success for >98% of children with pediatric CAP. The required dose to achieve the desired outcomes may change if beta-lactam resistance in pneumococcus increases.

Objective: Comparing the effectiveness of sequential and concurrent administration of albumin and furosemide in reducing edema in children with nephrotic syndrome.

Method: A double blinded randomized controlled clinical trial was conducted in patients diagnosed with nephrotic syndrome between 2 and 15 years of age. The patients were randomly divided into 2 groups of 32 subjects. One group received an admixture of albumin and furosemide, and the other received furosemide immediately after the albumin infusion. The weight loss and urinary sodium concentration results were analyzed in each group.

Results: The comparison of the 2 groups demonstrated that the group that received albumin and furosemide sequentially had statistically significant weight loss. There was no significant difference in the amount of urinary sodium, as determined by random spot urine analysis in 9 subjects in each group, and no study drug-associated adverse effects were observed in any patient.

Conclusions: there was a significant difference between weight loss in the 2 groups that received albumin and furosemide simultaneously or sequentially and according to this study, the sequential method of furosemide administration after albumin infusion is the preferred method to reduce edema in pediatric patients with nephrotic syndrome.

Valproic acid, carbamazepine and topiramate have well-known teratogenic risk and all 3 rank among the top 10 teratogenic medications with the highest prenatal exposure risk. Importantly, pregnancies exposed to valproic acid are not dominated by patients with epilepsy but rather with less serious conditions such as migraine. In the United States, only a weight loss combination product containing topiramate has a mandatory pregnancy prevention program, a so-called Risk Evaluation and Mitigation Strategy (REMS), while prevention of fetal exposure to all three single ingredient products relies on information in the product labeling and a medication guide provided at dispensing. REMS have been avoided for antinconvulsants because of concerns about reduced medication access for patients with serious conditions such as epilepsy, hence weighting maternal harm due to uncontrolled disease against adverse pregnancy or infant outcomes. However, the broad and growing spectrum of indications for all three medications, paired with increasingly strict abortion laws that may not allow pregnancy termination if accidental fetal exposure occurs, may require re-assessment of the benefit-risk of REMS. Here we argue that formal quantitative approaches are needed that allow assessments of maternal and infant risk, considering maternal disease, adverse pregnancy outcomes and teratogenic effects on infants, and the overall public health impact of REMS for anticonvulsants. For valproic acid, given its broad use, high risk of fetal exposure, and profound impact on child health, we predict the public health impact of a REMS will be favorable.

Procedural sedation in children has the propensity to result in costly hospital admissions and prolonged lengths of stay in emergency departments due to the coordination and resources required for completion. The use of intranasal (IN) dexmedetomidine in children for procedural sedation has been growing in popularity and demand in many clinical settings. Dexmedetomidine is a centrally acting alpha-2 agonist with anesthetic and anxiolytic properties, making it a useful option for sedation. Additional benefits of its use in the pediatric emergency department include high tolerability, decreased emotional distress of children, and ease of administration without need for parenteral access. Of the 18 pediatric patients who received IN dexmedetomidine for procedural sedation, 10 patients had successful procedural sedation solely with IN dexmedetomidine use. The success rate with IN dexmedetomidine was 63% for non-painful procedures (magnetic resonance imaging [MRI], computed tomography [CT]) and 57% for painful procedures (eye examinations, laboratory draw/intravenous [IV] placement, fracture reduction, foreign body removal). There were no documented adverse events with IN dexmedetomidine. Of the 18 patients, only 1 patient needed to return for a repeated scan and 2 patients were admitted owing to sedation needs. The use of IN dexmedetomidine in the pediatric emergency department provides a safe and less invasive option for sedation than commonly used sedatives. This leads to a reduced need for admissions dedicated to obtaining procedural sedation.

Objective: This study evaluated the chemical compatibility of N-acetylcysteine (NAC) and ondansetron to simplify the treatment of acute nausea and vomiting during intravenous (IV) NAC administration. NAC is commonly used to treat acetaminophen overdose, but its 21-hour IV infusion is often interrupted for ondansetron administration, which can pose risks.

Methods: High-performance liquid chromatography with ultraviolet detection was used to quantify NAC. To simulate IV administration, a closed-circuit pump with multiple independent lines, was plumbed with Y-sites to circulate NAC at concentrations matching 30- and 100-kg loading doses and 4-mg ondansetron was pushed into the flow paths. Control lines without ondansetron were also maintained. Samples were collected at 10, 20, and 30 minutes postondansetron introduction. NAC concentrations in single-drug and combination lines were compared using an unpaired t-test with Welch's correction (p = 0.05).

Results: The mean concentrations for the 100-kg dose were 55.23 and 55.28 mg/mL for control and with ondansetron, respectively. The 30-kg cohort included 36.38 mg/mL for control and 36.49 mg/mL with ondansetron. The results of the unpaired t-test for either weight illustrated that no statistical significance was achieved. Furthermore, the t-values of 0.2013 for 100 kg and 0.8556 for 30 kg support a less likely chance of significant difference.

Conclusion: Based on this experiment, ondansetron can be introduced into an NAC infusion via IV push in vitro without affecting the NAC concentration in the solution. The likelihood of IV compatibility for NAC and ondansetron could permit no infusion interruptions, reducing unnecessary risk of acetaminophen toxicity.

The purpose of this review is to define "neonatal selective serotonin reuptake inhibitor (SSRI) withdrawal syndrome" (NSWS) from a developmental perspective and outline its management strategies as described in the current body of literature, with a focus on pharmaceutical interventions. A literature search was conducted with PubMed, OVID Medline, Google Scholar, Embase, and Web of Science. Search terms included neonatal and SSRI combined with the Boolean operator "AND" coordinated with the terms withdrawal, poor neonatal adaptation, and neonatal abstinence syndrome. Non-pharmacologic interventions include appropriate hydration, nutrition, and providing a quiet and soothing environment for the infant. Most treatment algorithms for neonatal withdrawal syndromes involve in utero exposure to opioids and other psychotropics, and it is rare to find one that outlines specific guidelines for the management of NSWS. Symptomatic pharmacologic management should be individualized to the patient. Potential measures can include the administration of clonidine for tachycardia, hypertension, diaphoresis, and restlessness; phenobarbital for seizures; or chlorpromazine for agitation and irritability. There is generally no role for the use of morphine or methadone in the treatment of NSWS without combined exposure to opioids in utero. Without studies specifically designed to understand NSWS and guidelines on treatment, there is a lack of clarity regarding the management of neonates with this syndrome. There are limited data differentiating NSWS from neonatal opioid withdrawal despite these disease states being caused by different pharmaceutical agents. There needs to be clear and comprehensive guidelines inclusive of newer studies and comparative treatment efficacies to promote evidence-based practices surrounding NSWS.

Objective: Celiac disease and gluten sensitivities are on the rise, with a greater prevalence of the condition in children than adults. Resources to ascertain gluten content exist but can be incomplete and focus on medications for adults. The objective of this research is to determine gluten-free status of the top 100 pediatric medications dispensed.

Methods: The top 100 pediatric medications were identified by using Optum Clinformatics Data Mart database. After list creation, manufacturers and National Drug Code (NDC) for each drug were procured and used to contact manufacturers directly for gluten content information.

Results: Evaluation of 689 NDCs was completed with 50.2% of medications documented to be gluten-free. Additional categories were confirmed gluten-free but cannot confirm cross-contamination (22.6%), cannot confirm gluten-free (25.7%), and contains gluten (1.5%). Resource tables were developed from findings though information may change, based on manufacturing ingredients and processing.

Conclusions: Pediatric medications differ in gluten content, compared with medications for adults. Incomplete information exists regarding gluten content of medications, especially pediatric resources. Development of a pediatric-specific resource for gluten content of commonly dispensed medications in children and adolescents will hopefully benefit patients with celiac disease.

In the field of epilepsy, the advent of precision medicine and the repurposing of medications for new applications have fortuitously allowed more accurate diagnosing and individually targeted therapeutics. Despite these advances, there remain patients who do not respond sufficiently-or at all-to traditionally prescribed treatments. Clinicians often need to be creative, using clinical experience and rigorous research to intuit the next step when most, if not all, anti-seizure treatments have not produced sufficient results. Herein we describe 5 medications with emerging reports of efficacy for seizure control identified by coauthor clinical experience and prescribers in clinical practice for drug information purposes (e.g., ketamine, memantine, quinidine, riluzole, trazodone). Additionally, we summarize pertinent pharmacokinetics, adverse effects, and known and potential interactions with neurologically focused medications to further guide clinical application. Ketamine and memantine appear to be promising options to apply to patients presently, while quinidine, riluzole, and trazodone have data that could contribute to future applications in specific patient populations.