An Open-Label Study to Describe the Pharmacokinetics of Acyclovir in Premature Infants

Determining the appropriate dose of acyclovir for premature infants requiring treatment for herpes virus infection in order to prevent devastating consequences.

This study, completed in 2014, evaluated the safety and pharmacokinetics (PK) of intravenous acyclovir in premature infants with suspected systemic infection. Twenty infants, ≤34 weeks gestation, participated in the study for up to 13 days at two centers. The Pediatric Trials Network ultimately generated PK and safety data to change the package insert for acyclovir and guide dosing for premature infants.

Brian Smith, MD, MPH, MHS, of Duke Clinical Research Institute, discusses an open-label study to describe the pharmacokinetics of acyclovir in premature infants.

Summary

Infants have immature immune systems and are at high risk for serious infections caused by bacteria, viruses, or fungi. Because these infections can have severe consequences, doctors frequently give antimicrobial therapy to infants who are suspected of having an infection, even without definitively knowing the source of infection.

Acyclovir is approved by the U.S. Food and Drug Administration for herpes simplex virus (HSV) infections in infants. HSV is a very serious infection in this vulnerable group, often resulting in death or profound mental retardation. However, appropriate dosing of acyclovir had not been adequately studied in premature infants, meaning that doctors had to make educated guesses about the dosing of this potentially life-saving drug.

In this study, 20 premature infants (<35 weeks gestation at birth and <45 days of age) with suspected HSV infections were enrolled. We administered acyclovir to the infants to determine the levels of acyclovir in each. This allowed us to determine the appropriate dose of acyclovir in this understudied population.

Publications

Population pharmacokinetics of intravenous acyclovir in preterm and term infants.
Sampson MR, Bloom BT, Lenfestey RW, Harper B, Kashuba AD, Anand R, Benjamin DK Jr, Capparelli E, Cohen-Wolkowiez M, Smith PB.
Pediatric Infectious Diseases Journal • January 2014, volume 33, issue 1, pages 42-49.
PMCID: PMC3904301 [Free PMC article]

Presentations

Pediatric Academic Societies Annual Meeting, May 5-8, 2018

Dose-Safety Relationship for Acyclovir in the Treatment of Neonatal Herpes Simplex Virus
Ericson JE, Benjamin DK Jr, Boakye-Agyeman F, Raiola F, Adler-Shohet F, Laughon M, Poindexter B, Payne E, Zhao J, Kaneshige K, Harper B, Smith PB, on behalf of the Best Pharmaceuticals for Children Act – Pediatric Trials Network

Pediatric Academic Societies Annual Meeting, April 25-28, 2015

Safety of High-Dose Acyclovir in Infants
Ericson JE, Gostelow M, Autmizguine J, Clark RH, Benjamin DK Jr, Hornik CP, Smith PB, on behalf of the Best Pharmaceuticals for Children Act – Pediatric Trials Network Administrative Core Committee

Pediatric Academic Societies Annual Meeting, April 28-May 1, 2012

Population Pharmacokinetics of Acyclovir in Preterm and Term Infants
Krystle Perez, Kim Chantala, Amy H. Herring, P. Brian Smith, Reese H. Clark, Daniel K. Benjamin Jr., Michael Cohen-Wolkowiez, Matthew Laughon

Safety of Acyclovir in Hospitalized Infants
Simon B. Ascher, Daniel K. Benjamin Jr., C. Michael Cotten, Christoph P. Hornik, Michael Cohen-Wolkowiez, Reese H. Clark, and P. Brian Smith

OVERVIEW

Status:
Completed, clinical study report submitted to FDA

ClinicalTrials.gov identifier:
NCT00942084

Principal Investigators:
P. Brian Smith, MD, MPH, MHS and Daniel K. Benjamin, MD, PhD, MPH
Duke Health, Durham, NC

NEWS

  • Acyclovir PK study is complete October 2, 2013 The PTN open-label study to describe the pharmacokinetics (PK) of acyclovir in premature infants has concluded, with results recently published in the Pediatric Infectious Diseases Journal. Acyclovir is a drug used to treat herpes simplex virus (HSV) infections in infants. HSV is a very serious infection in those <6 months of age, often resulting in death ...
  • PTN acyclovir trial locks its database November 29, 2012 On September 19, 2012, the PTN locked the database for its trial of the pharmacokinetics of acyclovir in infants. Database lock means that all clinical trial data have been reviewed, queries have been resolved and issues addressed, and the database cannot be altered in any way. Acyclovir is approved by the U.S. Food and Drug Administration ...
  • PTN Acyclovir Trial Completes Enrollment November 29, 2012 On June 1, 2012, the PTN completed enrollment into its trial of the pharmacokinetics of acyclovir in infants. Acyclovir is approved by the U.S. Food and Drug Administration for herpes simplex virus (HSV) infections in babies. HSV is a very serious infection in this vulnerable group, often resulting in death or profound mental retardation. To date, ...