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

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 and morphine, 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.