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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Subjects Roux-en-Y-gastric bypass (RYGB) | Experimental | Sustained release morphine sulfate, 30 mg |
|
| Control volunteers matched with RYGB | Active Comparator | Sustained release morphine sulfate, 30 mg |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sustained release morphine sulfate, 30 mg | Drug | A single oral administration of a capsule of sustained release morphine sulfate, 30 mg, on one day. |
|
| Measure | Description | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | |
| Time of the maximum plasma concentration [Tmax] of morphine, morphine-3-glucuronide, morphine-6-glucuronide |
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Inclusion Criteria:
RYGB Group (n=12) :
Control group (n=12) :
Same characteristics
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jean-Francois JB Bergmann, MD, PhD | Hopital Lariboisiere | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Therapeutic Research Unit, Department of Internal Medicine, Hospital Lariboisiere | Paris | 75010 | France | |||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21295846 | Background | Finucane MM, Stevens GA, Cowan MJ, Danaei G, Lin JK, Paciorek CJ, Singh GM, Gutierrez HR, Lu Y, Bahalim AN, Farzadfar F, Riley LM, Ezzati M; Global Burden of Metabolic Risk Factors of Chronic Diseases Collaborating Group (Body Mass Index). National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9.1 million participants. Lancet. 2011 Feb 12;377(9765):557-67. doi: 10.1016/S0140-6736(10)62037-5. Epub 2011 Feb 3. | |
| 15616203 |
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| ID | Term |
|---|---|
| D009765 | Obesity |
| D010146 | Pain |
| ID | Term |
|---|---|
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
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|
| 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 | Blood samples gathered from hour 0,5 to hour 12 and urine sample gathered from the start to the end of the study visit. | 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 |
| 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 |
| 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 |
| Hopital Pitie Salpetriere |
| Paris |
| 75013 |
| France |
| Background |
| Sjostrom L, Lindroos AK, Peltonen M, Torgerson J, Bouchard C, Carlsson B, Dahlgren S, Larsson B, Narbro K, Sjostrom CD, Sullivan M, Wedel H; Swedish Obese Subjects Study Scientific Group. Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N Engl J Med. 2004 Dec 23;351(26):2683-93. doi: 10.1056/NEJMoa035622. |
| 21478461 | Background | Padwal RS, Gabr RQ, Sharma AM, Langkaas LA, Birch DW, Karmali S, Brocks DR. Effect of gastric bypass surgery on the absorption and bioavailability of metformin. Diabetes Care. 2011 Jun;34(6):1295-300. doi: 10.2337/dc10-2140. Epub 2011 Apr 8. |
| 19494810 | Background | Skottheim IB, Stormark K, Christensen H, Jakobsen GS, Hjelmesaeth J, Jenssen T, Reubsaet JL, Sandbu R, Asberg A. Significantly altered systemic exposure to atorvastatin acid following gastric bypass surgery in morbidly obese patients. Clin Pharmacol Ther. 2009 Sep;86(3):311-8. doi: 10.1038/clpt.2009.82. Epub 2009 Jun 3. |
| 22407114 | Background | Hamad GG, Helsel JC, Perel JM, Kozak GM, McShea MC, Hughes C, Confer AL, Sit DK, McCloskey CA, Wisner KL. The effect of gastric bypass on the pharmacokinetics of serotonin reuptake inhibitors. Am J Psychiatry. 2012 Mar;169(3):256-63. doi: 10.1176/appi.ajp.2011.11050719. |
| 24084922 | Background | Raebel MA, Newcomer SR, Reifler LM, Boudreau D, Elliott TE, DeBar L, Ahmed A, Pawloski PA, Fisher D, Donahoo WT, Bayliss EA. Chronic use of opioid medications before and after bariatric surgery. JAMA. 2013 Oct 2;310(13):1369-76. doi: 10.1001/jama.2013.278344. |
| 8491060 | Background | Hasselstrom J, Sawe J. Morphine pharmacokinetics and metabolism in humans. Enterohepatic cycling and relative contribution of metabolites to active opioid concentrations. Clin Pharmacokinet. 1993 Apr;24(4):344-54. doi: 10.2165/00003088-199324040-00007. |
| 9784932 | Background | Gourlay GK. Sustained relief of chronic pain. Pharmacokinetics of sustained release morphine. Clin Pharmacokinet. 1998 Sep;35(3):173-90. doi: 10.2165/00003088-199835030-00002. |
| 25141973 | Background | Lloret-Linares C, Hirt D, Bardin C, Bouillot JL, Oppert JM, Poitou C, Chast F, Mouly S, Scherrmann JM, Bergmann JF, Decleves X. Effect of a Roux-en-Y gastric bypass on the pharmacokinetics of oral morphine using a population approach. Clin Pharmacokinet. 2014 Oct;53(10):919-30. doi: 10.1007/s40262-014-0163-0. |
| 23338049 | Background | Buchwald H, Oien DM. Metabolic/bariatric surgery worldwide 2011. Obes Surg. 2013 Apr;23(4):427-36. doi: 10.1007/s11695-012-0864-0. |
| 19493300 | Background | Padwal R, Brocks D, Sharma AM. A systematic review of drug absorption following bariatric surgery and its theoretical implications. Obes Rev. 2010 Jan;11(1):41-50. doi: 10.1111/j.1467-789X.2009.00614.x. Epub 2009 Jun 2. |
| 20445535 | Background | Skottheim IB, Jakobsen GS, Stormark K, Christensen H, Hjelmesaeth J, Jenssen T, Asberg A, Sandbu R. Significant increase in systemic exposure of atorvastatin after biliopancreatic diversion with duodenal switch. Clin Pharmacol Ther. 2010 Jun;87(6):699-705. doi: 10.1038/clpt.2010.32. Epub 2010 May 5. |
| 19824817 | Background | Roberts DL, Dive C, Renehan AG. Biological mechanisms linking obesity and cancer risk: new perspectives. Annu Rev Med. 2010;61:301-16. doi: 10.1146/annurev.med.080708.082713. |
| 10201674 | Background | Lotsch J, Weiss M, Ahne G, Kobal G, Geisslinger G. Pharmacokinetic modeling of M6G formation after oral administration of morphine in healthy volunteers. Anesthesiology. 1999 Apr;90(4):1026-38. doi: 10.1097/00000542-199904000-00016. |
| 14663457 | Background | Kharasch ED, Hoffer C, Whittington D, Sheffels P. Role of P-glycoprotein in the intestinal absorption and clinical effects of morphine. Clin Pharmacol Ther. 2003 Dec;74(6):543-54. doi: 10.1016/j.clpt.2003.08.011. |
| D001835 |
| Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009461 | Neurologic Manifestations |