Pharmacokinetics of intravenous acetaminophen and its metabolites in morbidly obese patients

Completed

Conditions: obesity or overweight
10017998

Registration Number: NL-OMON37478

Lead Sponsor: Sint Antonius Ziekenhuis

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 28

Inclusion Criteria

Inclusion criteria for morbidly obese patients:
- BMI > 40 kg/m2 undergoing bariatric surgery.
- 18 -60 years old
- ASA physical classification of II or III
- All racial and ethnic groups will be included;Inclusion criteria for normal weight patients:
- BMI between 18 and 25 kg/m2 undergoing general surgery
- 18 -60 years old
- ASA physical classification of I, II or III
- All racial and ethnic groups will be included

Exclusion Criteria

Exclusion criteria for all patient groups:
- Renal insufficiency identified by GFR < 60 ml/min/1.73m2
- Liver disease identified by liver function tests: ASAT, ALAT, prothrombin time, *-GT, bilirubin, creatinine, albumin and alkaline phosphatase (ALP) ( > 3 times upper limit of normal values)
- 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 (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 before the study (24 hours before study)

Study & Design

Study Type: Observational invasive

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Clearance (total, glucuronidation, sulphation, CYP2E1 oxidation and unchanged)<br /><br>and volume of distribution of acetaminophen in morbidly obese patients in<br /><br>comparison with normal weight patients.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>- Difference in clearance (total, glucuronidation, sulphation, CYP2E1<br /><br>oxidation) and volume of distribution of acetaminophen in morbidly obese<br /><br>patients at the time of bariatric surgery and 0.5 * 2 year after bariatric<br /><br>surgery.<br /><br>- Liver function tests (ASAT, ALAT, prothrombin time, gamma- GT, bilirubin,<br /><br>creatinine and albumin) in morbidly obese patients in comparison with normal<br /><br>weight patients.<br /><br><br /><br><br /><br>Other endpoints that will be measured:<br /><br>- Total body weight, length and fat (free) mass<br /><br>- Insulin resistance: homa IR (fasting insulin and glucose levels)<br /><br>- Lipid levels: free fatty acids, triglycerides, cholesterol<br /><br>- Inflammation markers: TNF-alfa, IL-6, leptin, adiponectin en CRP<br /><br>- Metabolomic profile</p><br>