Acetaminophen Dosing in Obese Adolescents

Study Overview
=================
Brief Summary
-----------------
Although there are numerous studies investigating the pharmacokinetic properties of intravenous acetaminophen in infants and children with normal weight, there are none in the obese pediatric patient . This study will investigate the pharmacokinetics and pharmacodynamics of acetaminophen (total Cl and Vd) in obese children and adolescents

Detailed Description
-----------------
Obesity represents one of the most important public health issues according to the World Health Organization. It has reached epidemic proportions globally, with approximately 1.5 billion overweight adults aged 20 years and older and at least 600 million of them clinically obese .Childhood obesity is particularly problematic, because the co morbid disease states which accompany early obesity may require frequent pharmacotherapy and/or surgical intervention. Many of the metabolic and cardiovascular complications of obesity may also be present during childhood. Despite increased pharmacotherapy among obese patients, there is a paucity of dosing guidelines for this population. Optimal drug dosing in obese pediatric patients has not been explored as the present data available is specific for obese adults. Acetaminophen is one of the most commonly used medications in pediatric patients. Although there are numerous studies investigating the pharmacokinetic properties of intravenous acetaminophen in infants and children with normal weight there are none in the obese pediatric patient . This study will investigate the pharmacokinetics and pharmacodynamics of acetaminophen (total clearance and volume of distribution in obese children and adolescents

Official Title
-----------------
The Pharmacokinetics of Intravenous Acetaminophen and Its Metabolites in Obese Children and Adolescents

Conditions
-----------------
Obesity, Childhood

Intervention / Treatment
-----------------
* Drug: Tylenol


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participant will be a Children's National Health System (CNHS) inpatient or outpatient admitted for at least 24 hours observation as part of the surgical plan of care. Age range will be between 10 and 18. BMI% will be calculated using height and weight and will include the 5th-85th% (normal weight) and greater than or equal to 95th %.( obese weight) ASA physical classification of I, II or III. All racial and ethnic groups will be included Exclusion Criteria: Any patient that is pregnant or lactating. Renal insufficiency identified by GFR <60 ml/min/1.73m2 and/or creatinine > 3 times upper limit of normal values Liver disease identified by : AST, ALT, γ-GT, bilirubin, albumin and AlkP and PT > 3 times upper limit of normal values Patients with Gilbert-Meulengracht Syndrome Chronic alcohol intake or use of alcohol within last 72 hours Patients who are treated with drugs know to effect CYP2E1(inhibition: dithiocarb and disulfiram. Induction: isoniazid) and UGT (UDP-glucuronyltransferases) (induction: estradiol-containing contraceptives, carbamazepine, phenobarbital, phenytoin, mesuximide, oxcarbazepine, rifampicin, primidone, atazanavir / ritonavir, lopinavir / ritonavir, olanzapine, retigabine , nevaripine, efavirenz, saquinavir, nelfinavir, lamotrigine, felbamate, zonisamide, bupropion. Inhibition: valproic acid) Diabetes mellitus type II patients Smoking Acetaminophen intake up to 24 hours before enrollment. Acetaminophen allergy

Ages Eligible for Study
-----------------
Minimum Age: 10 Years
Maximum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Determine the single dose pharmacokinetics of acetaminophen and its metabolites (glucuronide, sulphate, cystein and mercapturic acid) in obese children and adolescents
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tylenol Dosing<br>Dosing of Tylenol for postoperative pain relief will include: children < 16 years; 650 mg every 6 hours, max 2.6 gram per 24 hours and children > or equal to 16 years every 6 hours 1 g of acetaminophen, max 4 gram per 24 hours). | Drug: Tylenol<br>* Dosing of Tylenol for post operative pain control<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Systemic clearance of acetaminophen and its metabolites (glucuronide, sulphate, cystein and mercapturic acid) in adolescent surgical patients |  | up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate postoperative pain management using the numerical rating scale system. |  | up to 3 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Acetaminophen, Obesity, Anesthesia, Adolescent