Obesity
Conditions
Keywords
drug metabolizing enzymes and drug transporter, Roux-en Y-Gastric Bypass, Obesity, Drug Availability, BMI over 35kg/m² and comorbidities or >40kg/m²
Brief summary
The activity of drug-metabolizing enzymes and transporters evolutes after Roux-en-Y gastric Bypass. Primary aim : To study the intra individual evolution of phenotypical markers of different drug metabolizing enzymes and one transporter (CYP1A2, CYP2D6, CYP2C9, CYP2C19, CYP3A4 and P-gp), using a cocktail phenotypic approach, after Roux-en-Y gastric Bypass.
Detailed description
Principal Judgement criteria : Phenotypical markers of enzymes and transporter activity before, at 5-8 weeks and 25-30 weeks following surgery. Secondary judgement criteria : * Genetic polymorphisms known to affect expression and/or activity of enzymes and transporter. * Intestinal and hepatic expression and activity of the enzymes and transporter of interest. * Markers of inflammation Methodology, study design : open-labelled monocentric study. Sample size : It will be a descriptive experimental study involving 12 subjects. Study design : In centre 1: Inclusion at least 2 weeks prior to surgery (V0) In centre 2: Three studies of 12 hours each will occur (in addition with the usual clinical and surgical follow up) at three times periods: in the 8 weeks period before surgery (V1), at 5-8 weeks after surgery (V2) and at 25-30 weeks after surgery (V3). In centre 3: the patients will undergo gastric bypass surgery (corresponding to the usual clinical and surgical follow up) and samples of jejunum and liver will be obtain during the surgery (J0). Centres 4 and 5 are involved in samples analysis.Hence, patients will attend 3 visits, in addition to the usual clinical and surgical follow-up. Study duration: 26 months (with duration of inclusion of 18 months) Duration for a patient: 38 weeks at maximum (8 months) Investigating center and participating units: one center enrolling the patients and three centers involving in the others investigations.
Interventions
DRUGphenotypical approach
each visit : CAFEINE : (solution orale) 2 ampoules de 2 ml = 100 mg de CAFEINE DEXTROMETHORPHANE : 15 ml de sirop contains 20 mg =\>22,5 ml = 30mg Midazolam : (solution injectable, ampoule 1 ml = 1 mg) : deux ampoules = 2 mg Digoxine nativelle (solution injectable, ampoule de 0.5mg) : 1 ampoule per os = 0.5 mg Losartan 50 mg : 1cp de 50mg
Sponsors
Ministry of Health, France
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Patients with morbid obesity (IMC \> 40 kg/m²) or severe obesity (IMC=35-40 kg/m²) with co morbidities (sleep apnea syndrome or hypertension without treatment or steatosis hepatitis) candidates for a gastric bypass. * Patient not receiving more than two treatments whose effect on the expression of enzymes and drug transporters is zero other than vitamins. * Patient agreeing to participate at three studies of one day (12 hours) occurring at three different periods. * Patients aged between 18 and 60 years old. * Patient giving its well-informed and free consent. * Patient without allergy to any of the drugs used for test. * Patients living in France during the study and with French social security
Exclusion criteria
* Tabacco * Contraception including estrogens compounds * Medication other than vitamins. * Allergy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phenotypical markers of enzymes and transporter activity | at 5-8weeks | plasmatic \[Paraxanthine/caffeine\] ratio (T4H) at 5-8 weeks following surgery. - plasmatic \[Omeprazole/5-hydroxyomeprazole\] ratio (T4H) at 5-8 weeks following surgery. - urinary Log (dextromethorphan/dextrorphan) (T0-T8h) at 5-8 weeks following surgery. - urinary Losartan/ E-3174 (T0-8h) at 5-8 weeks following surgery. - plasmatic AUC 0-inf midazolam at 5-8 weeks following surgery. - plasmatic AUC 0-inf digoxin at 5-8 weeks following surgery |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Intestinal and hepatic expression and activity of the enzymes and transporter of interest and markers of inflammation | before surgery | Intestinal and hepatic expression and activity of the enzymes and transporter of interest and markers of inflammation |
Countries
France
Outcome results
None listed