Bypass Complications
Conditions
Keywords
obesity, Roux-en-Y-gastric bypass, pharmacokinetics, Pain, morphine
Brief summary
The purpose of this study is to determine whether sustained release morphine pharmacokinetics parameters in patients undergone roux-en-y gastric bypass (RYGB) differ from subjects who did not. Our hypothesis is that exposure is comparable. Indeed, in the Study OBEMO (Determinants of Oral Morphine Answer Among Obese Patients Before and After Gastric Bypass; NCT00943969) the investigators observed changes in pharmacokinetics parameters for immediate release morphine, probably due to an earlier absorption of the morphine, in agreement with the expected clinical effect of this formulation.
Detailed description
This is an open label study with two arms: patients undergone roux-en-y gastric bypass and volunteers who did not matched by sex, age and Body Mass Index (BMI). In the pharmacokinetic visit the subject takes an oral administration of sustained release morphine, 30 mg, then 11 samples are collected during 12 hours.
Interventions
DRUGSustained release morphine sulfate, 30 mg
A single oral administration of a capsule of sustained release morphine sulfate, 30 mg, on one day.
Sponsors
Hopital Lariboisière
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
RYGB Group (n=12) : * Subjects who undergone RYGB for at least 24 months * Stable weight since almost one year (or weight loss below 10kg over the last year) Control group (n=12) : * Volunteers subjects, matched for age, sex, and Body mass index * No history of bariatric surgery Same characteristics * Subjects volunteers for the study * Age 20-65 years * Written consent
Exclusion criteria
* Known allergy to morphine or naloxone * Patients not affiliated to the french social security system * Subjects yet recruited in a study with remuneration * Abnormalities in liver function Prothrombin ratio \<70% and/ or aspartate transaminase \> 5 times the usual values and/ or alanine aminotransferase \>5 times the usual values and/ or in renal function (creatinine clearance Modification of Diet in Renal Disease (MDRD) \< 60ml/ min * Respiratory insufficiency defined by an oximetry below 90% * Pregnancy and breastfeeding * Use of drugs contra-indicated or not advised with morphine: * Agonists-antagonists opioids ( buprenorphine, nalbuphine, pentazocine ), naltrexone * Alcohol intake \> 30g by day * Cough medicine morphine-like ( dextromethorphan, noscapine, pholcodine ) * Codeine, ethylmorphine * Other morphine agonist ( alfentanil, codeine, dextromoramide, dextropropoxyphene, dihydrocodeine, fentanyl, oxycodone, pethidin, phenoperidine, remifentanil, sufentanil, tramadol ) * Barbiturates, benzodiazepines * Rifampicin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Morphine area under the curve (AUC0-inf) after its oral administration according to the morphine concentration. | During the study visit: morphine concentration at time hour 0,5 ; hour 1; hour 1,5 ; hour 2; hour2,5; hour3; hour 4; hour 5; hour 6; hour 8; hour 12 after its oral administration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time of the maximum plasma concentration [Tmax] of morphine, morphine-3-glucuronide, morphine-6-glucuronide | During the study visit: concentrations at time hour 0,5 ; hour 1; hour 1,5 ; hour 2; hour2,5; hour3; hour 4; hour 5; hour 6; hour 8; hour 12 after morphine oral administration | — |
| Observed clearance [Cl/F] of morphine, morphine-3-glucuronide, morphine-6-glucuronide | During the study visit: concentrations at time 0,5h; 1h; 1,5h; 2h; 2,5h; 3h; 4h; 5h; 6h; 8h; 12h after morphine oral administration | Blood samples gathered from hour 0,5 to hour 12 and urine sample gathered from the start to the end of the study visit. |
| Area under ther curve [AUC] of morphine-3-glucuronide, morphine-6-glucuronide | During the study visit: concentration at time hour 0,5 ; hour 1; hour 1,5 ; hour 2; hour2,5; hour3; hour 4; hour 5; hour 6; hour 8; hour 12 after morphine oral administration | — |
| Plasma Half-Life [T1 /2] of morphine, morphine-3-glucuronide, morphine-6-glucuronide | During the study visit: concentrations at time hour 0,5 ; hour 1; hour 1,5 ; hour 2; hour2,5; hour3; hour 4; hour 5; hour 6; hour 8; hour 12 after morphine oral administration | — |
| Maximum plasma concentration [Cmax] of morphine, morphine-3-glucuronide, morphine-6-glucuronide | During the study visit: concentrations at time hour 0,5 ; hour 1; hour 1,5 ; hour 2; hour2,5; hour3; hour 4; hour 5; hour 6; hour 8; hour 12 after morphine oral administration | — |
| Observed Volume of distribution [Vd / F] of morphine, morphine-3-glucuronide, morphine-6-glucuronide | During the study visit: concentrations at time hour 0,5 ; hour 1; hour 1,5 ; hour 2; hour2,5; hour3; hour 4; hour 5; hour 6; hour 8; hour 12 after morphine oral administration | — |
Countries
France
Outcome results
None listed