Gaps in Drug Dosing for Obese Children: A Systematic Review of Commonly Prescribed Emergency Care Medications

Clinical Therapy • September 2015

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Rowe S, Siegel D, Benjamin DK Jr; Best Pharmaceuticals for Children Act – Pediatric Trials Network Administrative Core Committee.

Approximately 1 of 6 children in the United States is obese. This has important implications for drug dosing and safety because pharmacokinetic (PK) changes are known to occur in obesity due to altered body composition and physiologic mechanisms. Inappropriate drug dosing in an emergency setting can limit therapeutic efficacy and increase drug-related toxic effects for obese children.

Advances in Pediatric Pharmacology, Therapeutics, and Toxicology

Advances in Pediatrics August 2015

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Wang LA, Cohen-Wolkowiez M, Gonzalez D
The goal of this publication is to highlight important advancements made in the field of pediatric pharmacology, toxicology, and therapeutics from January 2012 to December 2013.

Drug Dosing and Pharmacokinetics in Children With Obesity: A Systematic Review

JAMA Peds • July 2015

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Harskamp-van Ginkel MW, Hill KD, Becker KC, Testoni D, Cohen-Wolkowiez M, Gonzalez D, Barrett JS, Benjamin DK Jr, Siegel DA, Banks P, Watt KM; Best Pharmaceuticals for Children Act–Pediatric Trials Network Administrative Core Committee.

Obesity affects nearly one-sixth of US children and results in alterations to body composition and physiology that can affect drug disposition, possibly leading to therapeutic failure or toxic side effects. The depth of available literature regarding obesity’s effect on drug safety, pharmacokinetics, and dosing in obese children is unknown.

Pharmacokinetics, Pharmacodynamics, and Safety of Lisinopril in Pediatric Kidney Transplant Patients: Implications for Starting Dose Selection

Clinical Pharmacology Therapy • July 2015

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Trachtman H, Frymoyer A, Lewandowski A, Greenbaum LA, Feig DI, Gipson DS, Warady BA, Goebel JW, Schwartz GJ, Lewis K, Anand R, Patel UD; Best Pharmaceuticals for Children Act-Pediatric Trials Network Administrative Core Committee.

Hypertension in pediatric kidney transplant recipients contributes to long-term graft loss, yet treatment options–including angiotensin-converting enzyme inhibitors–are poorly characterized in this vulnerable population. We conducted a multicenter, open-label pharmacokinetic (PK) study of daily oral lisinopril in 22 children (ages 7-17 years) with stable kidney transplant function. Standard noncompartmental PK analyses were performed at steady state.

Fluconazole population pharmacokinetics and dosing for prevention and treatment of invasive Candidiasis in children supported with extracorporeal membrane oxygenation

Antimicrobial Agents and Chemotherapy • June 2015

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Watt KM, Gonzalez D, Benjamin DK Jr, Brouwer KL, Wade KC, Capparelli E, Barrett J, Cohen-Wolkowiez M.

Candida infections are a leading cause of infectious disease-related death in children supported by extracorporeal membrane oxygenation (ECMO). The ECMO circuit can alter drug pharmacokinetics (PK); thus, standard fluconazole dosing may result in suboptimal drug exposures. The objective of our study was to determine the PK of fluconazole in children on ECMO. Forty children with 367 PK samples were included in the analysis.

Pharmacokinetics and safety of recently approved drugs used to treat methicillin-resistant Staphylococcus aureus infections in infants, children and adults

Expert Review of Clinical Pharmacology May 2015

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Gostelow M, Gonzalez D, Smith PB, Cohen-Wolkowiez M
Methicillin-resistant Staphylococcus aureus (MRSA) remains a significant cause of morbidity in hospitalized infants. Over the past 15 years, several drugs have been approved for the treatment of S. aureus infections in adults. The use of there majority of these drugs has extended into the treatment of MRSA infections in infants, frequently with minimal safety or dosing information. Here, we review current pharmacokinetic, safety, and efficacy data of these drugs with a specific focus in infants.

Simultaneous determination of trimethoprim and sulfamethoxazole in dried plasma and urine spots

Bioanalysis • May 2015

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Gonzalez D, Melloni C, Poindexter BB, Yogev R, Atz AM, Sullivan JE, Mendley SR, Delmore P, Delinsky A, Zimmerman K, Lewandowski A, Harper B, Lewis KC, Benjamin DK Jr, Cohen-Wolkowiez M; Best Pharmaceuticals for Children Act–Pediatric Trials Network Administrative Core Committee.

Trimethoprim-sulfamethoxazole (TMP-SMX) is an antimicrobial drug combination commonly prescribed in children and adults. The study objectives were to validate and apply an HPLC-MS/MS method to quantify TMP-SMX in dried plasma spots (DPS) and dried urine spots (DUS), and perform a comparability analysis with liquid matrices.

Editorial commentary: Fluconazole therapeutic drug monitoring in children with cancer: not today

Clinical Infectious Disease • December 2014

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Cohen-Wolkowiez M, Benjamin DK Jr.

This editorial focuses on insufficient fluconazole exposure in pediatric cancer patients and the need for therapeutic drug monitoring in critically ill children.

Use of opportunistic clinical data and a population pharmacokinetic model to support dosing of clindamycin for premature infants to adolescents

Clinical Pharmacology and Therapeutics • September 2014

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Gonzalez D, Melloni C, Yogev R, Poindexter BB, Mendley SR, Delmore P, Sullivan JE, Autmizguine J, Lewandowski A, Harper B, Watt KM, Lewis KC, Capparelli EV, Benjamin DK Jr, Cohen-Wolkowiez M; Best Pharmaceuticals for Children Act – Pediatric Trials Network Administrative Core Committee.

Clindamycin is commonly prescribed to treat children with skin and skin-structure infections (including those caused by community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA)), yet little is known about its pharmacokinetics (PK) across pediatric age groups. A population PK analysis was performed in NONMEM using samples collected in an opportunistic study from children receiving i.v. clindamycin per standard of care.

Pharmacokinetics of Antimicrobials in Obese Children

GaBI Journal • June 2014

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Sampson M, Cohen-Wolkowiez M, Benjamin D Jr, Capparelli E, Watt K.

Childhood obesity is common and results in substantial morbidity. The most commonly prescribed drugs in obese children are antibiotics. However, physiological changes associated with childhood obesity can alter antibiotic pharmacokinetics and optimal body size measures to guide dosing in this population are ill defined. This combination can result in therapeutic failures or drug-related toxicities. This review summarizes pharmacokinetic information for antibiotics in obese children and implications for dosing.