Safety and Pharmacokinetics of Multiple-Dose Metronidazole in Premature Infants (PTN Metro)

Evaluating the safety and dosing of metronidazole in premature infants for the treatment of serious infections.

This study evaluated the safety and pharmacokinetics (PK) of intravenous metronidazole in premature infants with suspected serious infection. Twenty-four participants, less than 32 weeks gestational age with suspected serious infection, participated in the study for up to 15 days at three centers. The Pediatric Trials Network generated PK data to guide dosing of metronidazole in premature infants using a simplified dosing regimen based on postmenstrual age.

Gregory Kearns, PharmD, PhD, of Children's Mercy Hospital Kansas City, discusses the PTN metronidazole study: clinical pharmacology in action.

Brian Smith, MD, MPH, of the Duke Clinical Research Institute, discusses the metronidazole in premature infants study.

Summary

Metronidazole is approved by the U.S. Food and Drug Administration for the treatment of adults with infections caused by anaerobic bacteria. Children and premature infants may be affected by these bacteria, too; therefore, doctors frequently give metronidazole to infants who are suspected of having an infection caused by anaerobic bacteria. However, the appropriate dose of metronidazole in premature infants is not well-known.

We enrolled 24 babies <32 weeks gestational age with suspected serious infection and administered metronidazole for up to five days, measuring the levels of metronidazole in each baby. With this information, we are able to determine the appropriate dose of metronidazole in premature infants. Because metronidazole likely behaves differently in premature infants than it does in term infants, older children, and adults, this study meets a public health need for better evidence in the treatment of of this vulnerable group.

Publications

Determining population and developmental pharmacokinetics of metronidazole using plasma and dried blood spot samples from premature infants.
Cohen-Wolkowiez M, Sampson M, Bloom BT, Arrieta A, Wynn JL, Martz K, Harper B, Kearns GL, Capparelli EV, Siegel D, Benjamin DK Jr, Smith PB; on behalf of the Best Pharmaceuticals for Children Act – Pediatric Trials Network.
Pediatric Infectious Diseases Journal • September 2013, volume 32, issue 9, pages 956-961.
PMCID: PMC3769518 [Free PMC article]

Intestinal fatty-acid binding protein and metronidazole response in premature infants.
Sampson MR, Bloom BT, Arrieta A, Capparelli E, Benjamin DK Jr, Smith PB, Kearns GL, van den Anker J, Cohen-Wolkowiez M.
Journal of Neonatal and Perinatal Medicine • January 2014, volume 7, issue 3, pages 223-228.
PMCID: PMC4225165 [Free PMC article]

OVERVIEW

Status:
Published; clinical study report submitted to FDA

ClinicalTrials.gov identifier:
NCT01222585

Principal Investigators:
Michael Cohen-Wolkowiez, MD, PhD and Daniel K. Benjamin, MD, PhD, MPH
Duke Health, Durham, NC

NEWS

  • DCRI researchers complete first drug study for Pediatric Trials Network January 23, 2012 DCRI investigators have completed the study of metronidazole, an anti-microbial agent frequently administered to infants suffering from necrotizing enterocolitis. The Duke Clinical Research Institute has completed its first drug trial conducted for the Pediatric Trials Network (PTN). Late last year (2011), DCRI investigators completed their study of metronidazole, an anti-microbial agent frequently administered to infants suffering from ...