title: Effect of a Roux-en-Y gastric bypass on the pharmacokinetics of oral morphine using a population approach.
abstract: OBJECTIVE
  Obesity and opioid use for chronic pain in obese individuals are both important public health concerns. The pharmacokinetics of oral morphine after Roux-en-Y gastric bypass (RYGB) are unknown. Therefore, we aimed to study the pharmacokinetics of oral morphine in morbidly obese patients before and after RYGB surgery, to identify the effects of RYGB and the subsequent reversal of morbid obesity on the pharmacokinetic parameters of morphine.
  
  
  METHODS
  The pharmacokinetics of oral morphine (30 mg) were studied in 30 obese patients before (Visit 1) and then 7-15 days (Visit 2) and 6 months (Visit 3) after RYGB. A population pharmacokinetic model was used to describe the time course of the plasma morphine concentration, to study the effect of RYGB on morphine pharmacokinetics and to estimate inter-patient variability.
  
  
  RESULTS
  The oral morphine time to maximum plasma concentration (t max) was twofold lower and maximum plasma concentration (C max) was 1.7 times higher at Visit 2, and t max was 7.5 times lower and C max 3.3 times higher at Visit 3 than at Visit 1. The mean oral morphine area under the plasma concentration-time curve (AUC) increased significantly (1.55-fold) between Visits 1 and 3. Changes in body mass index (BMI) after RYGB were clearly associated with decreased apparent oral morphine clearance and apparent central and peripheral morphine volumes of distribution. None of the other anthropometric parameters explained the inter-subject variability in morphine exposure better than BMI.
  
  
  CONCLUSIONS
  RYGB and the BMI reduction that followed it dramatically increased the rate of morphine absorption and slightly increased morphine exposure. The dose of immediate-release forms of morphine may be divided in obese patients after RYGB to prevent adverse events due to early and high morphine plasma peaks.
authors.affiliation: Inserm, UMR-S 1144 Université Paris Descartes-Paris Diderot, Variabilité de réponse aux psychotropes, Paris, France, celialloret@yahoo.fr.
authors.forename: Célia
authors.initials: C
authors.lastname: Lloret-Linares
authors.forename: Déborah
authors.initials: D
authors.lastname: Hirt
authors.forename: Christophe
authors.initials: C
authors.lastname: Bardin
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Bouillot
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Oppert
authors.forename: Christine
authors.initials: C
authors.lastname: Poitou
authors.forename: François
authors.initials: F
authors.lastname: Chast
authors.forename: Stéphane
authors.initials: S
authors.lastname: Mouly
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Scherrmann
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Bergmann
authors.forename: Xavier
authors.initials: X
authors.lastname: Declèves
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D015992:Body Mass Index; D005260:Female; D015390:Gastric Bypass; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009020:Morphine / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D009767:Obesity, Morbid / Q000097:blood / Q000150:complications / Q000378:metabolism* / Q000601:surgery; D010146:Pain / Q000097:blood / Q000150:complications / Q000188:drug therapy; D012890:Sleep / Q000187:drug effects; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D009020:Morphine