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.