Plasma concentrations of fluticasone propionate and budesonide following inhalation from dry powder inhalers by healthy and asthmatic subjects.
BACKGROUND
All currently available inhaled corticosteroids reach the systemic circulation and have the potential to produce adverse effects with long term use. This risk is often assessed by measuring the effect of different inhaled corticosteroids on the hypothalamic-pituitary-adrenal (HPA) axis in healthy subjects. Absorption of fluticasone propionate and its effects on the HPA axis are greater in healthy subjects than in subjects with moderately severe asthma, but we have failed to show any difference in morning budesonide plasma levels or systemic effects between healthy and asthmatic subjects following inhalation of budesonide. To provide more information on the absorption of fluticasone propionate and budesonide, we have compared the plasma levels of both drugs over 8 hours in healthy and asthmatic subjects.


METHODS
The area under the plasma concentration-time curves (AUC) and the maximum concentration (Cmax) of fluticasone propionate and budesonide after a single inhaled dose of each drug were compared in 12 healthy control subjects and 12 subjects with moderately severe asthma.


RESULTS
Peak plasma levels of budesonide occurred much earlier and were approximately 20-fold higher than those of fluticasone propionate in both healthy and asthmatic subjects. The AUC and Cmax for fluticasone propionate were lower by 307 (95% CI 62 to 522) pg/ml/h or 43% (p=0.02) and 52 (95% CI -11 to 115) pg/ml or 39% (p=0.1) in subjects with asthma compared with healthy control subjects. In contrast, the AUC and Cmax for budesonide were almost identical between the two groups (mean differences 826 (95% CI -1493 to 3143) pg/ml/h (p=0.5) and 157 (95% CI -1026 to 1339) pg/ml (p=0.8).


CONCLUSIONS
Following inhalation, healthy subjects have higher plasma levels of fluticasone propionate than subjects with asthma whereas budesonide plasma levels are similar in the two groups of subjects. Comparing the systemic effects of budesonide and fluticasone propionate in healthy subjects is unlikely to be relevant to subjects with asthma.
Harrison
T W
TW
Respiratory Medicine, Nottingham City Hospital, Nottingham NG5 1PB, UK. tharris2@nchr.org.uk
Tattersfield
A E
AE
D000280:Administration, Inhalation; D000730:Androstadienes / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D019540:Area Under Curve; D001249:Asthma / Q000097:blood* / Q000188:drug therapy; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D019819:Budesonide / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D016022:Case-Control Studies; D005260:Female; D000068298:Fluticasone; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D011208:Powders
D000730:Androstadienes; D001993:Bronchodilator Agents; D011208:Powders; D019819:Budesonide; D000068298:Fluticasone