Project Details

Pharmacokinetics of Clonidine Administered in the Infant Population

Ashley Stark, MD, MS

Summary

BACKGROUND: The incidence of neonatal abstinence syndrome (NAS) has risen substantially in the past several years in the NICU and once conservative measures have failed, NAS is treated with further opioid therapy, exposing the infant brain to further harm. As an adjunctive therapy, clonidine decreases the number of morphine doses and decreases the duration of treatment in term infants exposed to methadone or heroin with NAS and those receiving sedation. GAP: Despite the increase in usage and great potential for clinical impact, clonidine is not approved for use in infants by the FDA and a total of only 5 PK studies in the pediatric population have been published, with only one specifically in the neonatal population which did not include preterm infants. The overall goal of this project is to inform proper dosing recommendations for clonidine in the preterm and neonatal population and provide preliminary data for future safety and efficacy studies in infants. HYPOTHESIS: Hypothesis 1: Clearance of clonidine will be 50% higher in infants with postmenstrual age >40 weeks compared to infants with postmenstrual age <40 weeks. Hypothesis 2: The incidence of adverse events of clonidine will be <10%. Hypothesis 3: Neonatal Pain, Agitation and Sedation (N-PASS) and Finnegan scores will be at least 3 points lower in infants with clonidine concentrations >1.5 g/L compared to infants with concentrations ≤1.5 g/L. METHODS: We plan to include infants <12 months of age receiving clonidine per routine medical care using a sparse sampling approach.This is an open label PK study of clonidine, in which we will monitor for adverse events and record N-PASS and Finnegan scores throughout the duration of clonidine exposure and for the following 7 days after the conclusion of treatment. RESULTS: Pending. IMPACT: Our study will be the first PK study in infants to include those that are preterm and will allow us to recommend proper dosing for clonidine which will improve the safety and efficacy for use in infants. Website Link: Twitter: @AshleyStarkMD