Pharmacokinetics of Acetaminophen in Morbidly Obese Patients

Study Overview
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Brief Summary
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This study will investigate the pharmacokinetics of acetaminophen in morbidly obese patients versus normal weight patients. Specifically the different metabolic pathways of acetaminophen in morbidly obese adults will be investigated; glucuronidation, sulphation and CYP2E1 (cytochrome P450 2E1) oxidation

Official Title
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Pharmacokinetics of Intravenous Acetaminophen and Its Metabolites in Morbidly Obese Patients

Conditions
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Morbid Obesity

Intervention / Treatment
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* Drug: acetaminophen 2 g


Participation Criteria
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Eligibility Criteria
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Inclusion criteria for morbidly obese patients: BMI > 40 kg/m2 undergoing bariatric surgery. Patients between 18 - 60 years old ASA physical classification of II or III All racial and ethnic groups will be included Inclusion criteria for control group: BMI between 18 and 25 kg/m2 undergoing general surgery Patients between 18 - 60 years old ASA (American Society of Anesthesiology) physical classification of I, II or III All racial and ethnic groups will be included Exclusion criteria for all study arms: Renal insufficiency Liver disease Patients with Gilbert-Meulengracht syndrome Chronic alcohol intake or use of alcohol within last 72 hours Pregnancy or breastfeeding Patients who are treated with drugs know to affect CYP2E1 and UGT (UDP glucuronosyltransferase) Diabetes mellitus type II patients Smoking Acetaminophen intake before the study (24 hours before study)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: normal weight patients<br>normal weight patients receiving acetaminophen 2 g instead of 1 g | Drug: acetaminophen 2 g<br> <br> |
| Experimental: mobidly obese patients<br>morbidly obese patients receiving acetaminophen 2 g instead of 1 g | Drug: acetaminophen 2 g<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clearance (total, glucuronidation, sulphation, CYP2E1 oxidation and unchanged) of acetaminophen in morbidly obese patients in comparison with normal weight patients. |  | 24 hours | 
| Volume of distribution of acetaminophen in morbidly obese patients in comparison with normal weight patients. |  | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in clearance (total, glucuronidation, sulphation, CYP2E1 oxidation) of acetaminophen in morbidly obese patients at the time of bariatric surgery and at 0.5 - 2 year after bariatric surgery. |  | 8 hours | 
| Difference in volume of distribution of acetaminophen in morbidly obese patients at the time of bariatric surgery and at 0.5 - 2 year after bariatric surgery. |  | 8 hours | 
| Liver function tests in morbidly obese patients in comparison with normal weight patients. |  | 24 hours |