Codeine in Mechanically Ventilated Neonates
Information source: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Mechanically Ventilated Neonates,; Painful Procedures in Newborns
Intervention: Codeine (Drug)
Phase: Phase 1
Status: Recruiting
Sponsored by: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Official(s) and/or principal investigator(s): Jacob V Aranda, MD, PhD, Principal Investigator, Affiliation: State University of New York Downstate
Overall contact: Jacob V Aranda, MD, PhD, Phone: 718-270-3092, Email: jaranda@downstate.edu
Summary
The purpose of this study is to determine the absorption and bioavailability of codeine in
relation to postnatal (PNA) and postconceptional (PCA) age; determine the parent drug
(codeine), its active metabolites, their formation rates and their ratios in relation with
PCA and PNA; and identify relevant genetic polymorphisms of opioid metabolism in the study
population and their potential relationship to the biodisposition and pharmacodynamic
effects of codeine. The study population is intubated and mechanically ventilated infants
equal to or greater than 26 weeks gestational age at birth and less than 4 weeks postnatal
age.
Clinical Details
Official title: Absorption and Metabolism of Oral Codeine in Mechanically Ventilated Neonates
Study design: Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: The rate and extent of absorption of oral codeine, the ratios of the observed concentration of each metabolite to the observed concentration of parent drug and the formation and clearances of the metabolites.
Secondary outcome: Secondary outcomes include the additional PK parameters elimination half life, area under the curve and mean residence time.
Detailed description:
This proposal has its origins in a larger initiative to elucidate the pharmacological basis
for the interindividual differences observed in opioid responsiveness. Gaps in our knowledge
related to opioid disposition in newborns need to be addressed to complete the design of the
required overarching initiative in which age could be treated as a continuous variable
within a context of PK, PD and PG determinants. This proposal is designed to generate
preliminary data that addresses two issues. First, can newborns absorb enterally
administered codeine and is this ability determined by PCA or PNA age? The second relates to
the ability of newborn infants to catalyze those reactions required to metabolically
activate both codeine and morphine. The latter will also be evaluated within the context of
PCA versus PNA age.
These data will not only fill an information gap that must be addressed before the larger
initiative moves forward, but they also provide a platform for serious study of the ontogeny
of certain pharmacokinetic processes that may prove critical to our understanding of newborn
drug disposition. In this way, codeine can provide important insights concerning the
ontogeny of drug disposition and permit the determination of the relative importance of PCA
versus PNA ages to the functional expression of these processes.
Eligibility
Minimum age: N/A.
Maximum age: 30 Days.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Neonates ≥ 26 weeks PCA receiving mechanical ventilation and painful procedure will
be eligible for participation in the study
- Subject's parent/legal guardian must give written informed consent prior to study
participation
- Subject is receiving opioid analgesia therapy based on caregiver determination. The
ideal patient will not be receiving morphine.
- Must be able to receive an enteral dose of codeine.
Exclusion Criteria:
- Known hypersensitivity to morphine, fentanyl, or codeine
- Patients with ALT concentrations >2x upper limit of normal for age or clinical
evidence of hepatic failure
- Patients with serum creatinine concentrations >2x upper limit of normal for age or
clinical evidence of renal failure
- Patients who are NPO
- Babies born to maternal drug abuse.
- Total serum bilirubin level of > 10 mg/dl or 170 umol/L.
Locations and Contacts
Jacob V Aranda, MD, PhD, Phone: 718-270-3092, Email: jaranda@downstate.edu
State University of New York Downstate, Brookyln, New York 11203, United States; Recruiting
Additional Information
Starting date: August 2008
Last updated: February 7, 2012
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