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Methylene blue: effects and disposition in sheep.

G E Burrows

    Journal of Veterinary Pharmacology and Therapeutics
    |September 1, 1984
    PubMed
    Summary

    Methylene blue pharmacokinetics in sheep were studied. Sodium nitrite altered distribution but not elimination, and methylene blue showed minimal toxicity, suggesting safe dosage increases for methemoglobinemia treatment.

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    Area of Science:

    • Pharmacokinetics and Toxicology
    • Veterinary Medicine
    • Biochemistry

    Background:

    • Methylene blue is used to treat methemoglobinemia.
    • Understanding its disposition and toxicity is crucial for safe therapeutic use.

    Purpose of the Study:

    • To determine the pharmacokinetics and urinary excretion of methylene blue in sheep.
    • To assess the toxicologic profile of methylene blue, including LD50, methemoglobin production, and hematologic effects.
    • To evaluate the influence of sodium nitrite on methylene blue pharmacokinetics.

    Main Methods:

    • Intravenous administration of methylene blue (15 mg/kg) to mature female sheep.
    • Comparison of methylene blue administered alone versus after sodium nitrite (50 mg/kg).
    • Pharmacokinetic analysis of elimination rate constant and distribution.
    • Toxicologic assessment including LD50 determination, methemoglobin production, and hematologic monitoring.

    Main Results:

    • Sodium nitrite significantly altered methylene blue distribution but not its overall elimination rate (beta = 0.0076 +/- 0.0016 min-1).
    • Minimal urinary excretion of intact or leucomethylene blue was observed.
    • Methylene blue exhibited low toxicity: minimal methemoglobin production at 50 mg/kg and no significant hematologic changes up to 30 mg/kg.
    • The 24-hour intravenous LD50 was determined to be 42.3 mg/kg.

    Conclusions:

    • Methylene blue pharmacokinetics in sheep are not significantly affected by sodium nitrite in terms of elimination.
    • Methylene blue demonstrates a favorable safety profile in sheep, with minimal adverse effects observed.
    • Dosage of methylene blue can potentially be safely increased up to 15 mg/kg for treating severe methemoglobinemia in veterinary settings.

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