Pharmacokinetics

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

Posted on by Kayla Korzekwinski

Pediatric Drugs • October 2018

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Shakhnovich V, Brian Smith P, Guptill JT, James LP, Collier DN, Wu H, Livingston CE, Zhao J, Kearns GL, Cohen-Wolkowiez M; Best Pharmaceuticals for Children Act–Pediatric Trials Network.

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.

A pharmacokinetic model for amiodarone in infants developed from an opportunistic sampling trial and published literature data

Posted on by Kayla Korzekwinski

Journal of Pharmacokinetics and Pharmacodynamics • June 2018

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Dallefeld SH, Atz AM, Yogev R, Sullivan JE, Al-Uzri A, Mendley SR, Laughon M, Hornik CP, Melloni C, Harper B, Lewandowski A, Mitchell J, Wu H, Green TP, Cohen-Wolkowiez M.

Amiodarone is a first-line antiarrhythmic for life-threatening ventricular fibrillation or ventricular tachycardia in children, yet little is known about its pharmacokinetics (PK) in this population. We developed a population PK (PopPK) model using samples collected via an opportunistic study design of children receiving amiodarone per standard of care supplemented by amiodarone PK data from the literature.

Population Pharmacokinetics of Intramuscular and Intravenous Ketamine in Children

Posted on by Kayla Korzekwinski

The Journal of Clinical Pharmacology • April 2018

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Hornik CP, Gonzalez D, van den Anker J, Atz AM, Yogev R, Poindexter BB, Ng KC, Delmore P, Harper BL, Melloni C, Lewandowski A, Gelber C, Cohen-Wolkowiez M, Lee JH; Pediatric Trial Network Steering Committee.

Ketamine is an N-methyl D-aspartate receptor antagonist used off-label to facilitate dissociative anesthesia in children undergoing invasive procedures. Available for both intravenous and intramuscular administration, ketamine is commonly used when vascular access is limited. Pharmacokinetic (PK) data in children are sparse, and the bioavailability of intramuscular ketamine in children is unknown.

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

Posted on by Kayla Korzekwinski

The Journal of Pediatrics • February 2018

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Shakhnovich V, Smith PB, Guptill JT, James LP, Collier DN, Wu H, Livingston CE, Zhao J, Kearns GL; Best Pharmaceuticals for Children Act – Pediatric Trials Network.

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. 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.

Comparative Analysis of Ampicillin Plasma and Dried Blood Spot Pharmacokinetics in Neonates

Posted on by Kayla Korzekwinski

Therapeutic Drug Monitoring • February 2018

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Le J, Poindexter B, Sullivan JE, Laughon M, Delmore P, Blackford M, Yogev R, James LP, Melloni C, Harper B, Mitchell J, Benjamin DK Jr, Boakye-Agyeman F, Cohen-Wolkowiez M.

Dried blood spot (DBS) is a practical sampling strategy for pharmacokinetic studies in neonates. The utility of DBS to determine the population pharmacokinetics (pop-PK) of ampicillin, as well as accuracy versus plasma samples, was evaluated. An open-label, multicenter, opportunistic, prospective study was conducted in neonates.

Population Pharmacokinetics of Trimethoprim-Sulfamethoxazole in Infants and Children

Posted on by Kayla Korzekwinski

Antimicrobial Agents and Chemotherapy • December 2017

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Autmizguine J, Melloni C, Hornik CP, Dallefeld S, Harper B, Yogev R, Sullivan JE, Atz AM, Al-Uzri A, Mendley S, Poindexter B, Mitchell J, Lewandowski A, Delmore P, Cohen-Wolkowiez M, Gonzalez D; the Pediatric Trials Network Steering Committee.

Trimethoprim (TMP)-sulfamethoxazole (SMX) is used to treat various types of infections, including community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) and Pneumocystis jirovecii infections in children. Pharmacokinetic (PK) data for infants and children are limited, and the optimal dosing is not known. We performed a multicenter, prospective PK study of TMP-SMX in infants and children.

Population Pharmacokinetics of Dexmedetomidine in Infants

Posted on by Kayla Korzekwinski

Journal of Clinical Pharmacology • September 2017

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Greenberg RG, Wu H, Laughon M, Capparelli E, Rowe S, Zimmerman KO, Smith PB, Cohen-Wolkowiez M

Despite limited pharmacokinetic (PK) data, dexmedetomidine is increasingly being used off-label for sedation in infants. This study aimed to characterize the developmental PK changes of dexmedetomidine during infancy.

Use of Population Pharmacokinetics and Electronic Health Records to Assess Piperacillin-Tazobactam Safety in Infants

Posted on by Kayla Korzekwinski

The Pediatric Infectious Disease Journal • September 2017

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Salerno S, Hornik CP, Cohen-Wolkowiez M, Smith PB, Ku LC, Kelly MS, Clark R, Gonzalez D; Best Pharmaceuticals for Children Act–Pediatric Trials Network Steering Committee.

Piperacillin, in combination with tazobactam, is frequently used in infants for treating nosocomial infections, although safety data in this population are limited. Electronic health record (EHR) data can be used to evaluate drug safety in infants, but measures of drug exposure are lacking. To relate simulated piperacillin exposure with adverse events (AEs) in infants using EHR data, we identified infants discharged from 333 neonatal intensive care units managed by the Pediatrix Medical Group between 1997 and 2012.

Population Pharmacokinetics and Exploratory Pharmacodynamics of Lorazepam in Pediatric Status Epilepticus

Posted on by Kayla Korzekwinski

Clinical Pharmacokinetics • August 2017

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Gonzalez D, Chamberlain JM, Guptill JT, Cohen-Wolkowiez M, Harper B, Zhao J, Capparelli EV; Best Pharmaceuticals for Children Act – Pediatric Trials Network Steering Committee.

Lorazepam is one of the preferred agents used for intravenous treatment of status epilepticus (SE). We combined data from two pediatric clinical trials to characterize the population pharmacokinetics of intravenous lorazepam in infants and children aged 3 months to 17 years with active SE or a history of SE.

Pharmacokinetics of Clindamycin in Obese and Nonobese Children

Posted on by Kayla Korzekwinski

Antimicrobial Agents and Chemotherapy • March 2017

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Smith MJ, Gonzalez D, Goldman JL, Yogev R, Sullivan JE, Reed MD, Anand R, Martz K, Berezny K, Benjamin DK Jr, Smith PB, Cohen-Wolkowiez M, Watt K; Best Pharmaceuticals for Children Act—Pediatric Trials Network Steering Committee.

Although obesity is prevalent among children in the United States, pharmacokinetic (PK) data for obese children are limited. Clindamycin is a commonly used antibiotic that may require dose adjustment in obese children due to its lipophilic properties. We performed a clindamycin population PK analysis using data from three separate trials. A total of 420 samples from 220 children, 76 of whom had a body mass index greater than or equal to the 95th percentile for age, were included in the analysis. Compared to other metrics, total body weight (TBW) was the most robust measure of body size.