The pharmacokinetics and pharmacodynamics of @entity17013 were studied in healthy volunteers after inhalation. In the morning on the day the study began, volunteers inhaled 0.5 mg of @entity17013 with and without oral administration of charcoal, or 1 mg, 2 mg, and 3 mg of @entity17013 with concomitant administration of charcoal. A placebo group was used to assess the endogenous @entity701 , granulocyte, and lymphocyte baseline levels. @entity17013 plasma levels were determined by high-performance liquid chromatography using a tandem mass spectrometer as detector (HPLC/ @entity15 / @entity15 ). @entity701 plasma levels and differential white blood cell counts were obtained over 12 hours. An integrated pharmacokinetic/pharmacodynamic (PK/ @entity1726 ) model was applied to link the @entity17013 plasma concentrations with the effects on lymphocytes, granulocytes, and @entity701 . Maximum concentration levels of 3 to 9 ng/mL of @entity17013 were observed after 0.2 to 0.3 hours for all of the investigated doses. The terminal half-life ranged from 1.3 to 1.7 hours. There was no statistical difference between treatments in the presence or absence of orally administered charcoal. The pharmacokinetic/pharmacodynamic (PK/ @entity1726 ) models satisfactorily described the time-courses of the effects on granulocytes, lymphocytes, and @entity701 suppression. The resulting E50-values (concentrations to induce 50% of the maximum effect) concurred with the reported values of in vitro receptor binding affinities. The duration of the systemic effects were short because of the short half-life of the drug. Cumulative @entity701 suppression increased with dose administration and ranged from 20% to 36%. The PK/ @entity1726 simulations resulted in a smaller degree of @entity701 suppression for the drug administered at 10 PM. The cumulative change from baseline was slightly smaller for the effects on granulocytes and lymphocytes than those on @entity701 . This information promotes the comparison with other inhaled glucocorticoids.

Pharmacokinetic/pharmacodynamic evaluation of systemic effects of XXXX after inhalation.

@entity1726 :: ('OMIM:168600', 'Disease') :: ['PD'] @entity15 :: ('MESH:D009103', 'Disease') :: ['MS'] @entity701 :: ('MESH:D006854', 'Chemical') :: ['Cortisol', 'cortisol'] @entity17013 :: ('MESH:C007734', 'Chemical') :: ['flunisolide', 'Flunisolide']
@entity17013 :: (MESH:C007734,Chemical) :: ['flunisolide']
