Effect of a Roux-en-Y gastric bypass on the pharmacokinetics of oral morphine using a population approach.

Abstract

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. The pharmacokinetics of oral morphine (30mg) were studied in 30 obese patients before (Visit1) and then 7-15days (Visit2) and 6months (Visit3) 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. 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 Visit2, and t max was 7.5 times lower and C max 3.3 times higher at Visit3 than at Visit1. The mean oral morphine area under the plasma concentration-time curve (AUC) increased significantly (1.55-fold) between Visits1 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. 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.