Glucocorticoids inhaled, systemic availability

Systemic availability of inhaled glucocorticoids can be reduced in two ways. First, by using esters that reduced local absorption in the case of beclomethasone the dipropionate is used. Secondly, by using glucocorticoids that are extensively metabolized in the liver after absorption from the gut, such as fluticasone and budesonide. These strategies can be combined fluticasone is given as the ester fluticasone propionate. 

The systemic availability of an inhaled glucocorticoid represents the additive and complex combination of pulmonary and gastrointestinal drug absorption. Absorption is influenced by many factors, including delivery device, the use of a spacer, the particle size of the inhaled drug, and the absorption and metabolism of the swallowed drug (1). 

The effects of fluticasone 1500 micrograms/day and budesonide 1600 micrograms/day, both by dry powder inhalation, on three systemic markers (urinary concentrations of total cortisol metabolites, morning serum cortisol, and osteocalcin concentrations) have been investigated in 46 healthy and 31 asthmatic subjects (8). Urinary total cortisol metabolite concentrations represented the most sensitive marker of the systemic effects of inhaled glucocorticoids, and were lower in healthy subjects treated with fluticasone than in asthmatic patients, suggesting greater systemic availability of fluticasone in healthy subjects. A similar correlation... 

In receptor affinity studies, the f -epimer was twofold more active than the S-epimer. Because the C-21 hydroxy is free, budesonide is not a prodrug and is active as administered. Only 34% of the metered dose of inhaled budesonide reaches the lung. Systemically absorbed budesonide is highly protein bound and metabolized to 16a-hydroxyprednisolone and 6(3-hydroxybudesonide in the liver. Both metabolites have less than 1% of the glucocorticoid activity of the parent compound. Inhaled budesonide is excreted mainly as metabolites via both the feces (15%) and the urine (32%). Budesonide is available as a powder delivered through an aerosol or as a suspension for inhalation. 

---