Studies on the deposition, bioavailability and systemic activity of glucocorticoids in man

Sammanfattning: The local deposition, pharmacokinetics, and systemic activity of inhaled and intranasal glucocorticosteroids in different formulations and devices(ICSs) has been investigated. After nasal administration of the ICS budesonide (Bud), the systemic availability (F) was found to be significantly higher from an aqueous pump spray and from the powder inhaler Turbuhaler, than from a pressurized metered dose inhaler (pMDI), and the uptake process was slower and less complete with the pMDI formulation. Lung deposition of Bud from a pMDI plus Nebuhaler, and from Turbuhaler, was found to be twice as high as with a pMDI alone, whereas Ftotal was only about 50% higher. Thus, a larger proportion of Ftotal was derived from lung deposited Bud when using a pMDI plus Nebuhaler, spacer and Turbuhaler, than when using a pMDI. It was also found that the pMDI resulted in a significantly larger variability in lung deposition than Turbuhaler. In addition, a marked reduction in F was found when the pMDI canisters were not shaken properly before administration which confirms that the pMDI is very dependent on proper handling. Fluticasone propionate (FP), was found to accumulate in plasma during repeated dosing due to a slow systemic elimination. The accumulation is a probable explanation for the marked plasma cortisol suppression observed with repeated dosing within the clinical dose range. In conclusion, the present study has shown differences in local deposition, pharmacokinetics and systemic activity of inhaled glucocorticoid formulations, features which may contribute to differences in therapeutic properties.