Pharmacokinetics of budesonide and formoterol administered via 1 pressurized metered-dose inhaler in patients with asthma and COPD.
In 3 open-label studies, the systemic bioavailability of budesonide and formoterol administered via pressurized metered-dose inhaler (pMDI) or dry powder inhaler (DPI) formulations was evaluated in asthma (24 children, 55 adults) or chronic obstructive pulmonary disease (COPD; n = 26) patients. Treatments were administered at doses high enough to estimate pharmacokinetic parameters reliably. Two of the studies included an experimental budesonide pMDI formulation. In study 1 (asthma, adults), budesonide area under the curve (AUC) was 32% and 31% lower and maximal budesonide concentration (C(max)) 45% and 56% lower after budesonide/formoterol pMDI and budesonide pMDI versus budesonide DPI. Formoterol AUC and C(max) were 13% and 39% lower after budesonide/formoterol pMDI versus formoterol DPI. In study 2 (asthma, children), budesonide AUC and C(max) were 27% and 41% lower after budesonide/formoterol pMDI versus budesonide DPI + formoterol DPI. In study 3 (COPD/asthma, adults), budesonide AUC and C(max) were similar and formoterol AUC and C(max) 18% and 22% greater after budesonide/formoterol pMDI versus budesonide pMDI + formoterol DPI (COPD). Budesonide and formoterol AUC were 12% and 15% higher in COPD versus asthma patients. In conclusion, systemic exposure generally is similar or lower with budesonide/formoterol pMDI versus combination therapy via separate DPIs or monotherapy and comparable between asthma and COPD patients.
Tronde
Ann
A
AstraZeneca R&D Lund, SE-221 87, Lund, Sweden. Ann.Tronde@astrazeneca.com
Gillen
Michael
M
Borgström
Lars
L
Lötvall
Jan
J
Ankerst
Jaro
J
D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000328:Adult; D001249:Asthma / Q000188:drug therapy*; D001682:Biological Availability; D019819:Budesonide / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D002648:Child; D018592:Cross-Over Studies; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D004983:Ethanolamines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D005260:Female; D000068759:Formoterol Fumarate; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D036501:Metered Dose Inhalers; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D055815:Young Adult
D000318:Adrenergic beta-Agonists; D004338:Drug Combinations; D004983:Ethanolamines; D005938:Glucocorticoids; D019819:Budesonide; D000068759:Formoterol Fumarate