The Role of the Pediatric Pharmacist in Precision Medicine and Clinical Pharmacogenomics for Children.

With the initiatives by the National Institutes of Health and the US Food and Drug Administration, pharmacogenomics is transitioning from the laboratory to patient care. Nearly 200 drug products now contain pharmacogenomic information as part of their labeling; many of these products are commonly used in the pediatric population. Because pharmacogenomic testing can provide patient-specific predictors for drug response, pharmacists are positioned to assume a leadership role in pharmacogenomic testing, clinical interpretation of results, and recommendations for individualization of drug therapy.

Personalized medicines - are pharmacists ready for the challenge?

The field of personalized medicine affords multiple opportunities to pharmacists, and pharmacists have specific knowledge, skills and abilities that make them uniquely suited to advance the use of personalized medicine as a clinical tool. The pharmacy profession as a whole, however, has been slow to embrace the concept of clinical pharmacogenetics and is now facing a critical juncture that can potentially redefine the professional identity of the pharmacist. Before practice transformation can occur, however, it is important for our profession to ask and fully explore the following question: Are pharmacists ready for the challenge of personalized medicine? When assessing the readiness of pharmacy for personalized medicine, one must consider factors that are specific to the individual pharmacist as well as systematic considerations that allow pharmacists to successfully integrate personalized medicine into their individual practice area.

The Role of Megalin in the Transport of Gentamicin Across BeWo Cells, an In Vitro Model of the Human Placenta.

Aminoglycosides (AG) are known to readily cross the placenta, although the mechanisms responsible for placental transport have not been characterized. Megalin is expressed in human placenta, and it is reasonable to speculate, given its role in renal AG uptake, that it is similarly involved in placental transport. However, the role of megalin in placental AG uptake has not been established.

Megalin expression in human term and preterm placental villous tissues: effect of gestational age and sample processing and storage time.

Introduction: The aims of this study were to characterize megalin expression in human term and preterm placental villous tissues and to assess the impact of gestational age and sample storage on receptor expression.

Methods: Placental tissue samples were collected from pregnant women undergoing term and preterm Cesarean deliveries. Placental villous tissues were used to quantify megalin protein and mRNA expression by western blotting and quantitative polymerase chain reaction (q-PCR), respectively.

Challenges in the pharmacologic management of obesity and secondary dyslipidemia in children and adolescents.

The rise in childhood obesity has lead to an increased number of children with lipid abnormalities and the predominance of a combined dyslipidemic pattern characterized by a moderate-to-severe elevation in triglycerides, normal-to-mild mild elevation in LDL cholesterol and reduced HDL cholesterol. Although recently published National Heart, Lung and Blood Institute (NHLBI) guidelines represent a significant step forward in managing primary dyslipidemias in pediatric patients, there is still no general consensus regarding the pharmacologic treatment of obesity-related lipid abnormalities in children. The use of early pharmacologic intervention to control dyslipidemias and reduce cardiovascular risk in young children is only expected to increase given the steady increase in obesity and emergence of atherosclerotic disease in pre-adolescents.

Receptor-mediated endocytosis across human placenta: emphasis on megalin.

Receptor-mediated endocytosis plays an important role in the maternal-fetal transport of various nutrients and drugs across human placenta. Megalin, a 600 kDa endocytic receptor, is expressed in placental syncytiotrophoblasts and is thought to contribute to the transport functions of the placenta. However, the molecular mechanisms involved in megalin-mediated transplacental transport of most substrates have not yet been characterized.

Accuracy of six anthropometric skinfold formulas versus air displacement plethysmography for estimating percent body fat in female adolescents with phenylketonuria.

Background: The reliability of studies investigating biological and therapeutic factors that influence body composition in PKU patients depends on accurate anthropometric measurements.

Objective: To determine the precision of six anthropometric skinfold equations versus air displacement plethysmography (ADP) for predicting body fat (BF) percentage in female adolescents with PKU.

Design: Skinfold and ADP measurements were recorded from a cross section of 59 female patients with PKU, ages 10-19 years.

The role of the pediatric pharmacist in personalized medicine and clinical pharmacogenomics for children: pediatric pharmacogenomics working group.

With the initiatives by the National Institutes of Health and the Food and Drug Administration, pharmacogenomics has now moved from the laboratory to the patient bedside. Over 100 drug-products now contain pharmacogenomic information as part of their labeling. Many of these are commonly used in the pediatric population.

The essential research curriculum for doctor of pharmacy degree programs.

In 2008, the American College of Clinical Pharmacy appointed the Task Force on Research in the Professional Curriculum to review and make recommendations on the essential research curriculum that should be part of doctor of pharmacy (Pharm.D.) degree programs.

Urine collected from diapers can be used for 2-D PAGE in infants and young children.

Urinary proteomic profiling has potential to identify candidate biomarkers of renal injury in infants provided an adequate urine sample can be obtained. Although diapers are used to obtain urine for clinical evaluation, their use for proteomic analysis has not been investigated. We therefore performed feasibility studies on the use of diaper-extracted urine for 2-D PAGE.

Association of the histamine N-methyltransferase C314T (Thr105Ile) polymorphism with atopic dermatitis in Caucasian children.

Study Objective: To investigate potential associations between the histamine N-methyltransferase (HNMT) gene, HNMT, C314T (Thr105Ile) polymorphism and atopic dermatitis in a cohort of Caucasian children.

Design: Prospective, multicenter, genotype-association study.

Setting: Four academic, tertiary care medical centers within the Pediatric Pharmacology Research Unit network.

Six-month, prospective, longitudinal, open-label caffeine and dextromethorphan phenotyping study in children with growth hormone deficiency receiving recombinant human growth hormone replacement.

Background: Recombinant human growth hormone (r-hGH) is increasingly being used in children. Although growth hormone (GH) may alter the clearance of concomitantly administered medications, its effects on individual drug-metabolizing enzymes in children have not been characterized.

Objective: The goal of this study was to assess the activities of cytochrome P450 (CYP) 1A2, N-acetyltransferase 2, xanthine oxidase, and CYP2D6 in children with isolated idiopathic GH deficiency before and 3 and 6 months after initiation of r-hGH treatment.

Comparison of various urine collection intervals for caffeine and dextromethorphan phenotyping in children.

Caffeine and dextromethorphan have been used successfully both alone and in combination to assess phenotype and enzyme activity in children of various ages. Previous pediatric phenotyping studies with these agents have used varying durations of urine collection. However, the minimum duration required for accurate phenotypic assessment with these compounds in children remains unknown.

Activities of cytochrome P450 1A2, N-acetyltransferase 2, xanthine oxidase, and cytochrome P450 2D6 are unaltered in children with cystic fibrosis.

The activities of hepatic cytochrome P450 (CYP) 1A2, N-acetyltransferase 2 (NAT-2), xanthine oxidase (XO), and CYP2D6 were evaluated in 12 young children (aged 3-8 years) with mild cystic fibrosis (CF) and 12 age-matched healthy control subjects by use of standard caffeine and dextromethorphan phenotyping methods. Subjects were given 4 oz of Coca-Cola (approximately 35 mg caffeine) (The Coca-Cola Company, Atlanta, Ga) and a single 0.5-mg/kg dose of dextromethorphan.

Current status of gene therapy for cystic fibrosis pulmonary disease.

Cystic fibrosis (CF) is a common lethal genetic disorder that affects all ethnic populations; however, it is most prevalent in Caucasians. Intensive basic research over the last 20 years has resulted in a wealth of information regarding the CF gene, its protein product and the mutational basis of disease. This increased understanding has lead to the development of gene therapy for the treatment of CF pulmonary disease.

Verbal dyspraxia and galactosemia.

Classical galactosemia is an autosomal recessive disorder resulting from deficient galactose-1-phosphateuridyl transferase (GALT) activity. Verbal dyspraxia is an unusual outcome in galactosemia. Here we validated a simplified breath test of total body galactose oxidation against genotype and evaluated five potential biochemical risk indicators for verbal dyspraxia in galactosemia: cumulative percentage dose (CUMPCD) of (13)CO(2) in breath, mean erythrocyte galactose-1-phosphate, highest erythrocyte galactose-1-phosphate, mean urinary galactitol, and erythrocyte GALT activity.

Impaired recovery of hypothalamic-pituitary-adrenal axis function and hypoglycemic seizures after high-dose inhaled corticosteroid therapy in a toddler.

Background: Corticosteroids are the treatment of choice for children with persistent reactive airway disease. In these patients, taper and discontinuation of systemic therapy is often facilitated by transition to high-dose inhaled corticosteroid treatment.

Objective: To report a case of impaired hypothalamic-pituitary-adrenal (HPA) axis recovery and adrenal crisis associated with prolonged high-dose inhaled therapy after long-term systemic corticosteroid treatment.