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lar fluid revealed that inhalation of 5 (3 mg/ml aerosol)
References and notes
was equally effective to a 30-mg/kg dose ip. The mea-
sured peak concentrations of 5 in the plasma were of
33,800 and 27 ng/ml for ip and aerosol administration,
respectively. Aerosol administration thus leads to a
thousandfold reduced plasma exposure with equal effec-
tiveness in preventing airway inflammation. In another
study, IL-13 levels in the broncho-alveolar fluid of mice
treated with 30 mg/kg of 5 were reduced to levels com-
parable to mice treated with 10 mg/kg ip of montelukast.
This in vivo proof of concept confirmed our hypothesis
that C3a was a valid target to treat airway inflammation
and that aerosol administration is a promising mode of
administration to circumvent the PK issues of this class
of compounds (Fig. 3).
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In conclusion, rigidification of known scaffold 4 led to
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