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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Physiological disposition of aerosolized MK-679 in rats.

[14C]MK-679, a potent antagonist of leukotriene D4, was suspended in freon under pressure and sprayed into rat lungs through a tracheal cannula. The particle size of the drug was 1 to 5 microns, and the mean dose was 98.8 +/- 4.46 micrograms/rat. Time course studies indicate that MK-679 was slowly but efficiently absorbed from the lung, with only 6% of the dose remaining in the lung at 6 hr. Biliary excretion, the major route of elimination of aerosolized MK-679, accounted for 48% of the dose in 6 hr. Concentrations of the parent drug plateaued in plasma at 1 to 4 hr, and drug was not detectable in plasma at 6 hr. The parent drug accounted for 94% of the radioactivity in the lung, indicating no significant metabolism by lung tissue. The concentration of MK-679 after aerosol administration was higher in the lung and lower in plasma than after iv administration of the drug at 28 times the aerosol dose. The results of this study suggest that inhalation of MK-679 should be a considered route of administration for the treatment of asthma.[1]

References

  1. Physiological disposition of aerosolized MK-679 in rats. Tocco, D.J., deluna, F.A., Vadas, E., Lin, J.H. Drug Metab. Dispos. (1992) [Pubmed]
 
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