Metabolism and Toxicity of Acetaminophen

Study Overview
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Brief Summary
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The purpose of this study is to investigate how acetaminophen (APAP) is released into the urine and blood; to determine how the blood levels of acetaminophen and its breakdown products affect the preterm infant's health; to decrease adverse drug reactions; and to collect data on how the genetic make-up or characteristics affect how APAP is handled within the preterm infant. By taking several blood and urine samples during the study, we will be able to check the blood levels (called pharmacokinetics) of APAP in preterm babies.

Detailed Description
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Study procedures: The decision to replace standard intravenous morphine therapy with APAP will be made by the attending neonatologist. Length of participation: 60 hours. No patient will be prescribed the medication specifically for the study purposes in the study protocol.

Official Title
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Metabolism and Toxicity of Acetaminophen in Preterm Infants

Conditions
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Pain

Intervention / Treatment
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* Drug: Acetaminophen/APAP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Preterm and term neonates of both genders and all races a postnatal age of less than 28 days GA's of from 22 to less than 37 weeks an indwelling (peripheral or umbilical) arterial line a clinical indication for intravenous administration of pain relief medication Exclusion Criteria: Neonates with severe asphyxia grade III or IV intraventricular hemorrhage, major congenital malformations/facial malformations (e.g., cleft lip and palate), neurological disorders those receiving continuous or intermittent neuromuscular blockers clinical or biochemical evidence of hepatic renal failure (including systemic hypoperfusion)

Ages Eligible for Study
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Minimum Age: 22 Weeks
Maximum Age: 37 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: group 2 Pain management<br>In preterm and term neonates with a GA of 28 weeks or more a 15 mg/kg dose of APAP will be given every 8 hrs by an intravenous infusion over 30-minute. In preterm and term neonates with a GA of less than 28 weeks 15 mg/kg dose of APAP will be given every 12 hrs by an intravenous infusion over 30-minute | Drug: Acetaminophen/APAP<br>* In preterm and term neonates with a GA of 28 weeks or more a 15 mg/kg dose of APAP will be given every 8 hrs by an intravenous infusion over 30-minute. In preterm and term neonates with a GA of less than 28 weeks a 15 mg/kg dose of APAP will be given every 8 hrs by an intravenous infusion over 30-minute<br>* Other names: Tylenol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| primary endpoint PK analysis | Blood and urine levels of APAP and metabolites | 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Developmental stage | To assess both the magnitude and statistical significance of any evidence of relationship between developmental stage and toxicity-associated metabolite levels. The analyses will also hold constant APAP dose, BID or TID and possible confounding variables such as birth order, maternal smoking status, and maternal age. We will plot the relationship between stage of development and measures of APAP Metabolism, taken at different gestational and postnatal ages. A hierarchical, cross sectional time series models will be used. | 48 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acetaminophen, Preterm Infants