Acetaminophen Dosing in Obese Adolescents

Obesity, Childhood Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03192566
• Other study ID #: 00004651
• Status: Recruiting
• Phase: Phase 3
• Start date: August 2016
• Est. completion date: September 2025

Study information

• Verified date: February 2023
• Source: Children's National Research Institute
• Contact: Janelle Vaughns, MD
• Phone: 202-476-4165
• Email: jvaughns[@]childrensnational.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 6
• Est. completion date: September 2025
• Est. primary completion date: August 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 10 Years to 18 Years

Eligibility

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, ?-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

Related Conditions & MeSH terms

• Obesity, Childhood
• Pediatric Obesity

Intervention

Drug:
• Tylenol
Dosing of Tylenol for post operative pain control

Locations

Country	Name	City	State
United States	Childrens National Health System	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Children's National Research Institute

Country where clinical trial is conducted

United States, 

References & Publications (8)

Blouin RA, Warren GW. Pharmacokinetic considerations in obesity. J Pharm Sci. 1999 Jan;88(1):1-7. doi: 10.1021/js980173a. No abstract available. — View Citation

Cali AM, Caprio S. Obesity in children and adolescents. J Clin Endocrinol Metab. 2008 Nov;93(11 Suppl 1):S31-6. doi: 10.1210/jc.2008-1363. — View Citation

Cheymol G. Clinical pharmacokinetics of drugs in obesity. An update. Clin Pharmacokinet. 1993 Aug;25(2):103-14. doi: 10.2165/00003088-199325020-00003. — View Citation

Erstad BL. Which weight for weight-based dosage regimens in obese patients? Am J Health Syst Pharm. 2002 Nov 1;59(21):2105-10. doi: 10.1093/ajhp/59.21.2105. No abstract available. — View Citation

Flegal KM, Carroll MD, Kit BK, Ogden CL. Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999-2010. JAMA. 2012 Feb 1;307(5):491-7. doi: 10.1001/jama.2012.39. Epub 2012 Jan 17. — View Citation

Mohammed BS, Engelhardt T, Cameron GA, Cameron L, Hawksworth GM, Hawwa AF, McElnay J, Helms PJ, McLay JS. Population pharmacokinetics of single-dose intravenous paracetamol in children. Br J Anaesth. 2012 May;108(5):823-9. doi: 10.1093/bja/aes025. Epub 20 — View Citation

Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of obesity and trends in body mass index among US children and adolescents, 1999-2010. JAMA. 2012 Feb 1;307(5):483-90. doi: 10.1001/jama.2012.40. Epub 2012 Jan 17. — View Citation

Zuppa AF, Hammer GB, Barrett JS, Kenney BF, Kassir N, Mouksassi S, Royal MA. Safety and population pharmacokinetic analysis of intravenous acetaminophen in neonates, infants, children, and adolescents with pain or Fever. J Pediatr Pharmacol Ther. 2011 Oct — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Systemic clearance of acetaminophen and its metabolites (glucuronide, sulphate, cystein and mercapturic acid) in adolescent surgical patients		up to 3 years
Secondary	Evaluate postoperative pain management using the numerical rating scale system.		up to 3 years