Codeine in Mechanically Ventilated Neonates
| Status: | Completed |
|---|---|
| Healthy: | No |
| Age Range: | Any |
| Updated: | 8/29/2018 |
| Start Date: | August 2008 |
| End Date: | March 6, 2013 |
Absorption and Metabolism of Oral Codeine in Mechanically Ventilated Neonates
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.
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.
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.
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.
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.
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