Evaluating palatability in young children: a mini-review of relevant physiology and assessment techniques.

The palatability of pediatric pharmaceutical products plays a crucial role of influencing medication compliance. Rejection of unpalatable medications can potentially lead to treatment failure which can have immediate and delayed consequences. With advances in both the food and pharmaceutical industries, the systematic assessment of palatability has gained importance.

Utility of the C-pantoprazole breath test as a CYP2C19 phenotyping probe for children.

The C-pantoprazole breath test (PAN-BT) is a safe, noninvasive, in vivo CYP2C19 phenotyping probe for adults. Our objective was to evaluate PAN-BT performance in children, with a focus on discriminating individuals who, according to guidelines from the Clinical Pharmacology Implementation Consortium (CPIC), would benefit from starting dose escalation versus reduction for proton pump inhibitors (PPIs). Children (n = 65, 6-17 years) genotyped for CYP2C19 variants *2, *3, *4, and *17 received a single oral dose of C-pantoprazole.

Peppermint oil effects on the gut microbiome in children with functional abdominal pain.

Peppermint oil (PMO) is effective in the treatment of functional abdominal pain disorders, but its mechanism of action is unclear. Evidence suggests PMO has microbicidal activity. We investigated the effect of three different doses of PMO on gut microbiome composition.

Randomised trial: Peppermint oil (menthol) pharmacokinetics in children and effects on gut motility in children with functional abdominal pain.

Aims: Little is known regarding the pharmacokinetics and pharmacodynamics of menthol, the active ingredient in peppermint oil (PMO). Our aim was to investigate the pharmacokinetics of menthol at 3 dose levels in children and determine their effects on gut motility and transit.

Methods: Thirty children ages 7-12 years with functional abdominal pain underwent wireless motility capsule (WMC) testing.

Clearance of buprenorphine during pregnancy and neonatal outcomes.

Buprenorphine is emerging as the preferred pharmacologic treatment for opioid use disorder during pregnancy. We examined the relative plasma clearance of buprenorphine (BUP) across pregnancy. Pregnant women with opioid use disorder participating in a prospective, observational study from 2013 to 2016 on stress in pregnancy who were receiving BUP for opioid use disorder were included.

A Pilot Comparison of High- Versus Low-Tech Palatability Assessment Tools in Young Children.

Background: Medication refusal in children is largely driven by aversive taste profiles, which in turn influence adherence and therapeutic outcomes. However, there are no standardized methods for evaluating taste in young children. This study compares facial recognition technology with three hedonic visual scales in this population.

Granzyme B and miR-378a Interaction in Acetaminophen Toxicity in Children.

Background And Aim: Hepatic phase I drug-metabolizing enzymes CYP2E1, CYP1A2 and CYP3A4 catalyze the biotransformation of Acetaminophen (APAP) and are important in the mediation of toxicity. The potential role of other hepatic and non-hepatic Phase I enzymes in APAP toxicity has not been established.

Methods: PCR array containing 84 genes involved in phase I drug metabolism was examined in subgroups of hospitalized children for APAP overdose, categorized as no toxicity (ALT ≤ 45 IU/L, n=5) and moderate toxicity (ALT ≥ 500 IU/L, n=5).

Bioavailability testing of a newly developed clindamycin oral suspension in a pediatric porcine model.

Clindamycin's bitter taste and odor is known to affect treatment adherence in children. Recently, a formulation of clindamycin HCl complexed with ion exchange resin IRP 69 was shown to mask the bitter taste. Because of the potential benefit of this formulation for children, a pilot study using a porcine model was conducted to evaluate its relative bioavailability.

Evaluating metronidazole as a novel, safe CYP2A6 phenotyping probe in healthy adults.

Aims: CYP2A6 is a genetically polymorphic enzyme resulting in differential substrate metabolism and health behaviours. Current phenotyping probes for CYP2A6 exhibit limitations related to procurement (deuterated cotinine), toxicity (coumarin), specificity (caffeine) and age-appropriate administration (nicotine, NIC). In vitro, CYP2A6 selectively forms 2-hydroxymetronidazole (2HM) from metronidazole (MTZ).

How to Conduct Clinical Trials in Children: A Tutorial.

Despite a growing interest in, and commitment to, implementing pediatric clinical trials, approximately one in every five trials in children fails because of inappropriate study design, suboptimal experiment planning, or inadequate participant enrollment. This tutorial, presented from the perspectives of seasoned pediatric investigators, an experienced research coordinator, and an established pediatric clinical trials network, is designed to provide practical guidance for successfully implementing pediatric clinical trials at an academic center or another comparable institution.

Developmental Changes in Pharmacokinetics and Pharmacodynamics.

Effective drug therapy to optimally influence disease requires an understanding of a drug's pharmacokinetic, pharmacodynamic, and pharmacogenomic interrelationships. In pediatrics, age is a continuum that can and does add variability in drug disposition and effect. This article addresses the many important factors that influence drug disposition and effect relative to age.

A Population-Based Pharmacokinetic Model Approach to Pantoprazole Dosing for Obese Children and Adolescents.

Background And Aims: Pharmacokinetic data for proton pump inhibitors (PPIs), acid-suppression drugs commonly prescribed to children, are lacking for obese children who are at greatest risk for acid-related disease. In a recent multi-center investigation, we demonstrated decreased, total body weight adjusted, apparent clearance (CL/F) of the PPI pantoprazole for obese children compared with their non-obese peers. Subsequently, we developed a population-based pharmacokinetic (PopPK) model to characterize pantoprazole disposition and evaluated appropriate pantoprazole dosing strategies for obese pediatric patients, using simulation.

Obese Children Require Lower Doses of Pantoprazole Than Nonobese Peers to Achieve Equal Systemic Drug Exposures.

Objective: To assess appropriate pantoprazole dosing for obese children, we conducted a prospective pharmacokinetics (PK) investigation of pantoprazole in obese children, a patient population that is traditionally excluded from clinical trials.

Study Design: A total of 41 obese children (6-17 years of age), genotyped for CYP2C19 variants *2, *3, *4, and *17, received a single oral dose of pantoprazole, ~1.2 mg/kg lean body weight (LBW), with LBW calculated via a validated formula.

Targeted metabolomic profiling indicates structure-based perturbations in serum phospholipids in children with acetaminophen overdose.

Phospholipids are an important class of lipids that act as building blocks of biological cell membranes and participate in a variety of vital cellular functions including cell signaling. Previous studies have reported alterations in phosphatidylcholine (PC) and lysophosphatidylcholine (lysoPC) metabolism in acetaminophen (APAP)-treated animals or cell cultures. However, little is known about phospholipid perturbations in humans with APAP toxicity.

Hydroxycarbamide in children with sickle cell anaemia after first-dose vs. chronic therapy: pharmacokinetics and predictive models for drug exposure.

Aims: The purposes of this work were to: (1) compare pharmacokinetic (PK) parameters for hydroxycarbamide in children receiving their first dose (HC ) vs. those receiving chronic therapy (HC ), (2) assess the external validity of a published PK dosing strategy, and (3) explore the accuracy of dosing strategies based on a limited number of HC measurements.

Methods: Utilizing data from two prospective, multicenter trials of hydroxycarbamide (Pharmacokinetics of Liquid Hydroxyurea in Pediatric Patients with Sickle Cell Anemia; NCT01506544 and Single-Dose (SD) and Steady-State (SS) Pharmacokinetics of Hydroxyurea in Children and Adolescents with Sickle Cell Disease), plasma drug concentration vs.

Pharmacokinetics of two 6-mercaptopurine liquid formulations in children with acute lymphoblastic leukemia.

Background: A liquid formulation of 6-mercaptopurine (6-MP) was recently approved by the Food and Drug Administration (Purixan®) based on bioavailability (BA) data from healthy adults. We examined the pharmacokinetics (PK) and BA of 6-MP in children with acute lymphoblastic leukemia (ALL) comparing a marketed tablet, two extemporaneously prepared liquid formulations, and data from the approved liquid formulation.

Methods: Twenty-two children (6-17 years) participated in a randomized two-way, crossover study of two cohorts.

Palatability of a novel oral formulation of prednisone in healthy young adults.

Objectives: Prednisone is a widely used anti-inflammatory for a variety of conditions. While oral liquid formulations of prednisone enable weight-based dosing, children frequently find them to be objectionable due to bitter taste. This limitation of prednisone can adversely impact patient acceptance and may result in non-compliance.

Decreased Pregnane X Receptor Expression in Children with Active Crohn's Disease.

Expression of the pregnane X receptor (PXR) has been reported to be decreased in animal models of inflammatory bowel disease (IBD). To investigate the differential expression of PXR in children with Crohn's disease, a type of IBD, RNA was extracted from archived intestinal biopsies from 18 children with Crohn's disease (CD) and 12 age- and sex-matched controls (aged 7-17yrs). The aim of this investigation was to compare the relative mRNA expression of PXR, cytochrome p450 3A4 (CYP3A4), and villin 1 (VIL1) (a marker of epithelial cell integrity) in the inflamed terminal ileum (TI) versus noninflamed duodenum of children with CD.