Methylene blue: effects and disposition in sheep.
The disposition and urinary excretion pharmacokinetics of methylene blue were determined after its intravenous administration at 15 mg/kg to mature female sheep. Comparisons were made between methylene blue administered alone or subsequent to 50 mg/kg sodium nitrite. The overall elimination rate constant (beta) of methylene blue, 0.0076 +/- 0.0016 min-1, was not influenced by prior administration of sodium nitrite. However, the distribution rate was significantly altered by sodium nitrite. Very little of the methylene blue was eliminated in the urine either intact or as leucomethylene blue in spite of its relatively short half life. Toxicologic assessment was carried out using LD50 determination, methemoglobin production and hematologic effects as evaluation parameters. Methemoglobin production was minimal with doses as high as 50 mg/kg and no significant hematologic changes were seen up to 4 weeks after a total dose of 30 mg/kg methylene blue. The 24 h LD50 for intravenous methylene blue administered as a 3% solution was 42.3 mg/kg with 95% confidence interval limits of 37.3 to 47.9 mg/kg. From these data it appears that as conditions may warrant, the dosage of methylene blue may be safely increased up to at least 15 mg/kg in therapy of severe methemoglobinemias.
D000818:Animals; D005260:Female; D007700:Kinetics; D008706:Methemoglobin / Q000378:metabolism; D008751:Methylene Blue / Q000009:adverse effects / Q000378:metabolism* / Q000627:therapeutic use; D012756:Sheep / Q000378:metabolism*; D013053:Spectrophotometry / Q000379:methods
D008706:Methemoglobin; D008751:Methylene Blue