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Metabolic interaction between morphine and various benzodiazepines.

G M Pacifici, L L Gustafsson, J Säwe

    Acta Pharmacologica Et Toxicologica
    |April 1, 1986
    PubMed
    Summary

    Benzodiazepines inhibit morphine glucuronidation. Oxazepam was shown to reduce morphine glucuronide formation in rats, both in laboratory tests and in live animal studies.

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    Area of Science:

    • Pharmacology
    • Drug Metabolism
    • Toxicology

    Background:

    • Morphine is primarily metabolized via glucuronidation.
    • Benzodiazepines are commonly prescribed psychoactive drugs.
    • Understanding drug interactions is crucial for patient safety.

    Purpose of the Study:

    • To investigate the in vitro and in vivo interaction between benzodiazepines and morphine glucuronidation.
    • To determine the inhibitory potential of various benzodiazepines on morphine conjugation.

    Main Methods:

    • In vitro studies using rat liver microsomes to assess inhibition of morphine glucuronidation by benzodiazepines.
    • In vivo studies in rats involving pretreatment with oxazepam before morphine administration, followed by urine analysis.

    Main Results:

    • All tested benzodiazepines (diazepam, N-desmethyldiazepam, oxazepam, lorazepam, clonazepam, nitrazepam, flunitrazepam) inhibited morphine glucuronidation in vitro.
    • Clonazepam exhibited the strongest inhibition (86%), while nitrazepam showed the least (42%) at 1.5 mM.
    • Rats pretreated with oxazepam demonstrated a reduced morphine glucuronide/morphine ratio in urine, indicating in vivo inhibition.

    Conclusions:

    • Benzodiazepines are inhibitors of morphine glucuronidation.
    • Oxazepam inhibits morphine glucuronidation in rats, both in vitro and in vivo.
    • These findings highlight potential pharmacokinetic interactions between benzodiazepines and morphine.

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