Fluticasone elimination

In asthmatic human patients, fluticasone propionate improves asthma symptoms and parameters, improves pulmonary function and reduces pulmonary inflammation and airway reactivity (Barnes et al 1998). Regular fluticasone reduces or eliminates the need for rescue 2 agonist therapy and produces progressive improvement in airway reactivity and pulmonary function. In clinical studies, equivalent efficacy is demonstrated with one-quarter of the dose of fluticasone compared with flunisolide and budesonide, and equivalent efficacy is demonstrated with one-half of the dose of fluticasone compared with beclometasone. Adrenal function is less affected by fluticasone propionate at therapeutic doses than with beclometasone, flunisolide or budesonide. Although all aerosolized corticosteroids are considered safe, fluticasone has the least potential for adverse systemic effects and has the most favorable therapeutic index. 

This approach is robust because it does not rely on any pharmacokinetic assumptions and allows the characterization of absorption processes among different drugs if IV data are available. For example, differences in the absorption profiles between fluticasone propionate and budesonide can easily be identified with this method, while differences in fmax were not able to readily provide this information. The mean residence time without availability of intravenous data should not be used to compare absorption profiles of different drug entities, because it is also determined by the systemic elimination of the drug. This approach is, however, suitable for evaluating the differences of different formulations of the same drug. 

Although clearance is similar for most currently used inhaled glucocortico-steroids, vast differences in elimination half-life between inhaled glucocortico-steroids appear to exist. Huticasone, for which volume of distribution averages 12 L/kg and half-life ranges between 8 and 14 h has been shown to accumulate (52). The half-Ufe of fluticasone is substantially longer than that of triamcinolone or budesonide, having a half-life of only about 2 to 3 h (53). This difference in half-lives may explain the aforementioned difference in suppression of cortisol secretion between fluticasone and budesonide in healthy volunteers and in asthmatic patients observed after 3-5 days of treatment. 

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