Selecting the proper pediatric dose: It is more than size that matters

Kearns, Gregory L.

doi:10.1002/cpt.168

Cited by 17 publications

(18 citation statements)

References 10 publications

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“…Given the wide variability of ampicillin PK in infants, EHR data alone is unable to characterize the exposure safety relationship of the drug. (13) To overcome this limitation, we simulated ampicillin exposures using a population PK model developed from a cohort of infants enrolled in a PK study conducted by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Pediatric Trials Network. (14)…”

mentioning

confidence: 99%

Electronic Health Records and Pharmacokinetic Modeling to Assess the Relationship between Ampicillin Exposure and Seizure Risk in Neonates

Hornik

Benjamin

Smith

et al. 2016

The Journal of Pediatrics

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Objective To evaluate the relationship between ampicillin dosing, exposure, and seizures. Study design Retrospective observational cohort study of electronic health record (EHR) data combined with pharmacokinetic model derived drug exposure predictions. EHR from 348 Pediatrix Medical Group neonatal intensive care units from 1997 to 2012. All infants 24–41 weeks gestational age, 500–5400 g birth weight, first exposed to ampicillin prior to 25 days postnatal age. Using a 1-compartment pharmacokinetic model and her data, we simulated maximum ampicillin concentration at steady state (Cmaxss, µg/mL) and area under the concentration time curve from 0 to 24 hours (AUC24, µg*h/dL). Using multivariable logistic regression, we evaluated association between ampicillin dosing, exposure and seizures as documented in the EHR. Results We identified 131,723 infants receiving 134,041 courses of ampicillin for 653,506 infant-days of exposure. The median daily dose was 200 mg/kg/day (25th, 75th percentile; 100, 200). Median Cmaxss and AUC24 were 256.6 µg/mL (164.3, 291.5) and 2593 µg*h/dL (1917, 3334). On multivariable analysis, dosing was not associated with seizures. However increasing Cmaxss [Odds ratio (OR) = 1.10, (95% confidence interval (CI) 1.03, 1.17] and AUC24 [OR = 1.11, (95% CI 1.05, 1.18)] were associated with increased odds of seizures. Conclusions In this cohort of hospitalized infants, higher ampicillin exposure was associated with seizures as documented in the EHR.

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confidence: 99%

Electronic Health Records and Pharmacokinetic Modeling to Assess the Relationship between Ampicillin Exposure and Seizure Risk in Neonates

Hornik

Benjamin

Smith

et al. 2016

The Journal of Pediatrics

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“…In pediatrics, a wide array of body sizes is found. Body size is considered the most important predictor of CL and V . V generally increases linearly with body weight, whereas clearance generally increases nonlinear (Figure ).…”

Section: Part Ii: Pk Assessmentmentioning

confidence: 99%

“…In many cases, drug dosing for adults and children is correlated and extrapolation is possible . However, due to developmental changes in children, especially in infants and children below two years of age, these conditions might not be met …”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics and population pharmacokinetics in pediatric oncology

Sassen

Zwaan

Sluis

et al. 2019

Pediatric Blood & Cancer

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Pharmacokinetic research has become increasingly important in pediatric oncology as it can have direct clinical implications and is a crucial component in individualized medicine. Population pharmacokinetics has become a popular method especially in children, due to the potential for sparse sampling, flexible sampling times, computing of heterogeneous data, and identification of variability sources. However, population pharmacokinetic reports can be complex and difficult to interpret. The aim of this article is to provide a basic explanation of population pharmacokinetics, using clinical examples from the field of pediatric oncology, to facilitate the translation of pharmacokinetic research into the daily clinic.

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“…Substantial changes in organ function and enzyme processes that occur before and after birth through completion of puberty have major influences on drug disposition . Because age and body size are usually highly correlated, including organ size and functional capacity, age is a strong indicator of drug disposition …”

Section: Pediatric Dosage Adjustmentmentioning

confidence: 99%