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

Tor A Aasmundstad

National Institute of Forensic Toxicology, PO Box 9934 Ila, N-0132 Oslo, Norway

Per Størset

National Institute of Forensic Toxicology, PO Box 9934 Ila, N-0132 Oslo, Norway

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.

Key Words: interaction • human • metabolism • morphine • morphine-3-glucuronide • morphine-6-glucuronide

Human & Experimental Toxicology, Vol. 17, No. 6, 347-352 (1998)
DOI: 10.1177/096032719801700611
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