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Dose related changes in tissue morphine concentration.

E F Hahn, B I Norton, J Fishman

    Research Communications in Chemical Pathology and Pharmacology
    |April 1, 1976
    PubMed
    Summary
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    Morphine distribution in rats showed consistent blood-to-brain ratios across doses. However, the hypothalamus, kidney, and liver demonstrated increased morphine uptake with higher doses.

    Area of Science:

    • Pharmacology
    • Neuroscience
    • Toxicology

    Background:

    • Morphine is a potent opioid analgesic with complex pharmacokinetic properties.
    • Understanding morphine's tissue distribution is crucial for optimizing therapeutic use and managing side effects.

    Purpose of the Study:

    • To investigate the dose-dependent distribution of morphine in rat tissues.
    • To determine the blood-to-brain morphine ratio across a range of administered doses.

    Main Methods:

    • Rats were administered varying doses of radiolabeled morphine (morphine-6(3)H).
    • Tissue and blood samples were analyzed using a tissue oxidizer to quantify isotope levels.
    • The relative distribution of morphine between blood and brain was calculated.

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    Main Results:

    • A consistent blood-to-brain morphine distribution ratio of approximately 5.5:1 was observed across doses (0.07-10.0 mg/kg).
    • The hypothalamus showed disproportionately higher morphine uptake compared to other central tissues.
    • Kidney and liver exhibited the most significant dose-related increases in morphine uptake among peripheral tissues.

    Conclusions:

    • Morphine distribution into the brain is relatively constant despite dose variations.
    • Specific tissues like the hypothalamus, kidney, and liver show altered morphine accumulation at higher doses.
    • These findings highlight tissue-specific pharmacokinetics of morphine that may influence its central and peripheral effects.