Effects of obesity, non-alcoholic fatty liver disease and bariatric surgery on systemic cytochrome P450-mediated drug metabolism using a COCKTAIL approach.

Recruiting

Conditions: Obesitas
Obesity and non-alcoholic fatty liver disease
10019654

Registration Number: NL-OMON50513

Lead Sponsor: Academisch Medisch Centrum

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 17

Inclusion Criteria

In order to be eligible to participate in this study, a subject must meet the
following criteria:
- Capability to provide informed consent and to comply with the requirements
and restrictions listed on the informed consent form;
- Stable weight 3 months prior to inclusion;
- Obese, but otherwise healthy, with the exception of NAFLD, females, aged
between 18 - 45 years;
- Eligible and scheduled for laparoscopic RYGB surgery (in accordance with the
national guidelines (74)).

Exclusion Criteria

A potential subject who meets any of the following criteria will be excluded
from participation in this study:
- Any medical disorder (with the exception of NAFLD and metabolic syndrome);
- Major illness in the past 3 months;
- History of cholecystectomy or other bile duct anomalies;
- (History of) (an) eating disorder(s);
- Use of prescription or non-prescription drugs and herbal or dietary
supplements that affect the CYP enzymes of interest within 30 days prior to the
administration of the drug cocktail, except for oral contraceptives;
- Diabetes;
- Drug abuse or alcoholism (>2 units of alcohol per day);
- Strenuous exercise for at least 3 days prior to each study day, defined as
more than 1 hour of exercise per day;
- Difficulty in donating blood or limited accessibility of a vein;
- Use of tobacco products (induction of liver enzymes).

Study & Design

Study Type: Observational invasive

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary study endpoints are the differences in area under the plasma<br /><br>concentration versus time curve (AUC) for each drug following the<br /><br>administration of the cocktail in four different situations/ disease states:<br /><br>(1) early (= anatomical) and (2) late and (3) very late (= weight reduction<br /><br>dependent) post-RYGB surgery compared to the pre-RYGB surgery situation.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary endpoints include the differences in the PK parameters clearance,<br /><br>volume of distribution, absorption rate, mean residence time and elimination<br /><br>half-life in the above mentioned situations / disease states. </p><br>