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.

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.

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