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

Condition(s) targeted: Obesity

Intervention: gastric bypass (Procedure)

Phase: Phase 4

Status: Recruiting

Sponsored by: Hopital Lariboisière

Official(s) and/or principal investigator(s):
Célia LLoret Linares, Principal Investigator, Affiliation: Assistance Publique - Hôpitaux de Paris

Overall contact:
Célia Lloret Linares, MD, Phone: 00 33 1 49 95 65 19, Email: celialloret@yahoo.fr

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.

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

Study design: Other, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Pharmacokinetics Study

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

Secondary outcome:

Morphine and M6G AUC, clearance, Cmax and Tmax

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

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

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

Minimum age: 18 Years. Maximum age: 60 Years. Gender(s): Both.

Criteria:

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

Célia Lloret Linares, MD, Phone: 00 33 1 49 95 65 19, Email: celialloret@yahoo.fr

Unit of Therapeutic Research, Department of Internal Medicine, Lariboisière Hospital, Paris cedex 10 75475, France; Recruiting
Célia Lloret Linares, MD

Starting date: April 2009
Ending date: September 2010
Last updated: July 21, 2009