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) wh ich possess no opioid activity, and morphine-6-glucuronide (M6G) which is a potent opioid receptor agonist that probably contribute to the d esired as well as toxic effects of morphine. 2 In order to investigate the possible effect of ranitidine on morphine glucuronidation indicat ed by clinical studies and later confirmed in vitro, a double blind cr oss-over study on eight human volunteers administered oral morphine pl us ranitidine or placebo was conducted. 3 Urine was collected in fract ions for 24 h, Serum and urine samples were prepared by solid phase ex traction and morphine, M3G and M6G were quantified by HPLC. 4 Ranitidi ne significantly reduced the individual serum M3G/M6G ratio, and tende d to increase the serum AUC((0-90)) of morphine. In contrast, ranitidi ne had no significant effect on the urinary M3G/M6G ratio. The urinary recovery of morphine or morphine glucuronides was unaffected by ranit idine. 5 Possible explanations to the apparent incongruity between the serum and urine data are discussed.