Ta. Aasmundstad et P. Storset, INFLUENCE OF RANITIDINE ON THE MORPHINE-3-GLUCURONIDE TO MORPHINE-6-GLUCURONIDE RATIO AFTER ORAL-ADMINISTRATION OF MORPHINE IN HUMANS, Human & experimental toxicology, 17(6), 1998, pp. 347-352
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.