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J Pediatr. 2016 Nov;178:125-129.e1. doi: 10.1016/j.jpeds.2016.07.011. Epub 2016 Aug 10.

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

Author information

1
Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC; Department of Pediatrics, Duke University School of Medicine, Durham, NC. Electronic address: christoph.hornik@duke.edu.
2
Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC; Department of Pediatrics, Duke University School of Medicine, Durham, NC.
3
Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC.
4
Department of Pediatrics, University of California, San Diego, La Jolla, CA.
5
Deparment of Biostatistics and Bioinformatics, Duke University, Durham, NC; Skaggs School of Pharmacy, University of California, San Diego, La Jolla, CA.
6
Department of Pediatrics, Penn State University, Hershey, PA.
7
Pediatrix-Obstetrix Center for Research and Education, Sunrise, FL.

Abstract

OBJECTIVE:

To evaluate the relationship between ampicillin dosing, exposure, and seizures.

STUDY DESIGN:

This was a retrospective observational cohort study of electronic health record (EHR) data combined with pharmacokinetic model derived drug exposure predictions. We used the EHR from 348 Pediatrix Medical Group neonatal intensive care units from 1997 to 2012. We included 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 EHR 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/d (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 (OR = 1.10, 95% 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.

KEYWORDS:

ampicillin; dosing; exposure; infants; seizure

PMID:
27522443
PMCID:
PMC5085855
DOI:
10.1016/j.jpeds.2016.07.011
[Indexed for MEDLINE]
Free PMC Article

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