Determinants of Oral Morphine Answer Among Obese Patients Before and After Gastric Bypass

Hopital Lariboisière31 enrolled

Overview

The bariatric surgery is widely used to treat obesity. Roux-en-Y gastric bypass is one of the most frequently surgical methods performed and combines restrictive and malabsorptive procedures. Different data suggest that this surgery may modify drug absorption and we think it would be clinically relevant to describe the consequences of gastric bypass on drug systemic exposure in obese patients, since no data on the comparison between the pharmacokinetics (PK) of a drug before and after surgery are available and help to predict the drugs posology.The investigators decided to study the morphine because there is a lack of information about the PK, pharmacodynamics (PD) et pharmacogenetics (PG) of morphine in obese subjects, in contrary with anaesthetic drugs. This is a drug with a narrow therapeutic range frequently prescribed in obese patients.

Study Type

INTERVENTIONAL

Allocation

Masking

NONE

Enrollment

Conditions

Obesity

Interventions

gastric bypass

Eligibility

Sex: ALLMin age: 18 YearsMax age: 60 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Patients aged between 18 and 60 years old. * Patients with morbid obesity (IMC \> 40 kg/m²) or severe obesity (IMC=35-40 kg/m²) with co morbidities (sleep apnea syndrome or hypertension or steatosis hepatitis) with a favourable decision of a multidisciplinary team for a gastric bypass. * Patient agreeing to go 3 times for a one day hospitalisation in the URT of the Lariboisière Hospital for the morphine PK/PD. * Patient with a previous medical examination. * Patient giving its well-informed and free consent after information. Exclusion Criteria: * diabetes * concomitant sedative, antidepressive or analgesic treatments or drugs unadvised with morphine * untreated sleep apnea syndrom, hypoxia (PaO2\<70mmHg) or hypercapnia (PaCO2\>45mmHg), anaemia \<10g/dL, ASAT or ALAT\>3N

Outcomes

Primary Outcomes

30mg Oral morphine systemic exposure (AUC 0-24)

Time frame: Before surgery-7-15 days after surgery- 6 months after surgery

Secondary Outcomes

Morphine and M6G AUC, clearance, Cmax and Tmax

Time frame: Before surgery-7-15 days after surgery- 6 months after surgery

fat mass and total body water (assessed by DEXA and BIA)

Time frame: before surgery and 6 months following surgery

mRNA and protein expression of P-gp , UGT2B7, MRP2 and MRP3 in intestinal biopsies

Time frame: obtained from the bariatric surgery

genetic polymorphisms known to affect expression and/or activity of enzymes, receptors and transporters involved in morphine PK/PD (UGT2B7, P-gp, OPRM1, COMT) and morphine PK/PD

Time frame: Before surgery