Influence of ranitidine on the morphine-3- glucuronide to morphine-6-glucuronide ratio after oral administration of morphine in humans

Abstract

1 In humans morphine is metabolised to morphine-3- glucuronide (M3G) which possess no opioid activity, and morphine-6-glucuronide (M6G) which is a potent opioid receptor agonist that probably contribute to the desired as well as toxic effects of morphine.

2 In order to investigate the possible effect of ranitidine on morphine glucuronidation indicated by clinical studies and later confirmed in vitro, a double blind cross-over study on eight human volunteers administered oral morphine plus ranitidine or placebo was conducted.

3 Urine was collected in fractions for 24 h. Serum and urine samples were prepared by solid phase extraction andmorphine, M3G and M6G were quantified by HPLC.

4 Ranitidine significantly reduced the individual serum M3G/M6G ratio, and tended to increase the serum AUC₍₀ - 90) of morphine. In contrast, ranitidine had no significant effect on the urinary M3G/M6G ratio. The urinary recovery of morphine or morphine glucuronides was unaffected by ranitidine.

5 Possible explanations to the apparent incongruity between the serum and urine data are discussed.

Keywords

interaction human metabolism morphine morphine-3-glucuronide morphine-6-glucuronide

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