Influence of Morbid Obesity on the Pharmacokinetics of Morphine, Morphine-3-Glucuronide, and Morphine-6-Glucuronide

Clinical Pharmacokinetics
Sjoerd de HoogdCatherijne A J Knibbe

Abstract

Obesity is associated with many pathophysiological changes that may result in altered drug metabolism. The aim of this study is to investigate the influence of obesity on the pharmacokinetics of morphine, morphine-3-glucuronide (M3G), and morphine-6-glucuronide (M6G) through a combined analysis in morbidly obese patients and non-obese healthy volunteers. In this analysis, data from 20 morbidly obese patients [mean body mass index 49.9 kg/m2 (range 37.6-78.6 kg/m2) and weight 151.3 kg (range 112-251.9 kg)] and 20 healthy volunteers [mean weight 70.6 kg (range 58-85 kg)] were included. Morbidly obese patients received 10 mg of intravenous (I.V.) morphine after gastric bypass surgery, with additional morphine I.V. doses as needed. Healthy volunteers received an I.V. bolus of morphine of 0.1 mg/kg followed by an infusion of 0.030 mg kg-1 h-1 for 1 h. Population pharmacokinetic modeling was performed using NONMEM 7.2. In morbidly obese patients, elimination clearance of M3G and M6G was decreased substantially compared with healthy volunteers (p < 0.001). Regarding glucuronidation, only a slight decrease in the formation of M6G and a delay in the formation of M3G was found (both p < 0.001). Obesity was also identified as a covariate ...Continue Reading

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Citations

Nov 23, 2019·Scandinavian Journal of Pain·Amalie H SimoniAnne E Olesen
Feb 20, 2019·European Journal of Drug Metabolism and Pharmacokinetics·Joanna PorażkaEdmund Grześkowiak
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Methods Mentioned

BETA
gastric bypass
biopsy

Clinical Trials Mentioned

NCT01097148

Software Mentioned

Pirana
R
COMBOS
Psn
NONMEM
Xpose

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