The effect of morbid obesity on morphine glucuronidation.
The purpose of the present work was to study the change in morphine metabolic ratio in obese subjects before and after Roux-en-Y Gastric Bypass (RYGB) and to identify clinical and/or biological factors associated with this change. The pharmacokinetics (PK) of oral morphine (30mg), morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) was performed in patients before (n=25; mean BMI=43.2 (35.4-61.9)kg/m2), 7-15days (n=16) and 6 months after RYGB (n=19; mean BMI=32.3 (25.4-46.0)kg/m2). Morphine Cmaxand AUC0-infwere significantly increased and morphine Tmaxsignificantly shortened at 6 months after RYGB compared with preoperative data, indicating an important increase in the rate and extent of morphine absorption. The morphine metabolic ratio0-infM3G+M6G/Morphine, decreased significantly from the preoperative to 6 months postoperative period with an average of -26% (range -74%; +21%; p=0.004), but not in the immediate post-operative period. The change in morphine metabolic ratio was associated with a change in BMI, fat mass in kg, and triglyceride levels (rho=0.5, p≤0.04). The degree of change in several markers of low-grade inflammation, or the level of liver steatosis and fibrosis before surgery, was not associated with the change in morphine metabolic ratios. Our findings indicate that RYGB-induced weight loss significantly decreases morphine metabolic ratio, arguing for an effect of morbid obesity on glucuronidation. With glucuronide exposure at 6 months similar to preoperative values, a higher morphine AUC0-infshould encourage reducing morphine dosage in patients undergoing RYGB and chronically receiving immediate-release oral morphine.
Inserm, UMR-S 1144 Université Paris Descartes-Paris Diderot, Variabilité de réponse aux psychotropes, France; Assistance Publique-Hôpitaux de Paris, Hôpital Lariboisière, Therapeutic Research Unit, Department of Internal Medicine, Paris F-75010, France. Electronic address: celialloret@yahoo.fr.
Celia
C
Lloret-Linares
Inserm, UMR-S 1144 Université Paris Descartes-Paris Diderot, Variabilité de réponse aux psychotropes, France. Electronic address: xiaolong19891205@gmail.com.
Huilong
H
Luo
Assistance Publique-Hôpitaux de Paris, Hôpital Hôtel Dieu, Biostatistics and Epidemiology Department, Paris, France. Electronic address: alexandra.rouquette@aphp.fr.
Alexandra
A
Rouquette
Inserm, UMR-S 1144 Université Paris Descartes-Paris Diderot, Variabilité de réponse aux psychotropes, France; Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Pharmacokinetics and Pharmacochemistry Unit, Paris F-75014, France. Electronic address: laurence.labat@aphp.fr.
Laurence
L
Labat
Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, Service de Nutrition, Université Pierre et Marie Curie, Institut cardiométabolisme et nutrition (ICAN), Paris F-75013, France. Electronic address: christine.poitou-bernert@aphp.fr.
Christine
C
Poitou
Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, Service de Nutrition, Université Pierre et Marie Curie, Institut cardiométabolisme et nutrition (ICAN), Paris F-75013, France. Electronic address: joan.tordjman@crc.jussieu.fr.
Joan
J
Tordjman
Assistance Publique-Hôpitaux de Paris, Hôpital Ambroise Paré, Université Versailles Saint Quentin, Department of Surgery, Boulogne, France. Electronic address: jl.bouillot@aphp.fr.
Jean-Luc
JL
Bouillot
Inserm, UMR-S 1144 Université Paris Descartes-Paris Diderot, Variabilité de réponse aux psychotropes, France; Assistance Publique-Hôpitaux de Paris, Hôpital Lariboisière, Therapeutic Research Unit, Department of Internal Medicine, Paris F-75010, France. Electronic address: stephane.mouly@aphp.fr.
Stéphane
S
Mouly
Inserm, UMR-S 1144 Université Paris Descartes-Paris Diderot, Variabilité de réponse aux psychotropes, France. Electronic address: jm.scherrmann@fwidal.inserm.fr.
Jean-Michel
JM
Scherrmann
Inserm, UMR-S 1144 Université Paris Descartes-Paris Diderot, Variabilité de réponse aux psychotropes, France; Assistance Publique-Hôpitaux de Paris, Hôpital Lariboisière, Therapeutic Research Unit, Department of Internal Medicine, Paris F-75010, France. Electronic address: jf.bergmann@aphp.fr.
Jean-François
JF
Bergmann
Inserm, UMR-S 1144 Université Paris Descartes-Paris Diderot, Variabilité de réponse aux psychotropes, France; Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Pharmacokinetics and Pharmacochemistry Unit, Paris F-75014, France. Electronic address: xavier.decleves@aphp.fr.
Xavier
X
Declèves
D005260:Female; D015390:Gastric Bypass; D006801:Humans; D008297:Male; D009020:Morphine / Q000378:metabolism*; D009022:Morphine Derivatives / Q000378:metabolism*; D009767:Obesity, Morbid / Q000378:metabolism* / Q000601:surgery
D009022:Morphine Derivatives; C035349:morphine-6-glucuronide; D009020:Morphine; C018108:morphine-3-glucuronide
Bariatric surgery; Glucuronidation; Morphine; Obesity; Steatohepatitis