Pharmacokinetics of fluticasone propionate and salmeterol delivered as a combination dry powder via a capsule-based inhaler and a multi-dose inhaler
| Autor: | Robert Chan, Joseph Bianco, Rashmi Mehta, Margaret D. Louey, Kevin P. Jenkins, Peter T. Daley-Yates, Anastasia Stylianou |
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| Rok vydání: | 2014 |
| Předmět: |
Adult
Male Pulmonary and Respiratory Medicine animal structures Adolescent Pharmacology Fluticasone propionate Young Adult Pharmacokinetics Administration Inhalation Humans Medicine Pharmacology (medical) Sympathomimetics Glucocorticoids Asthma Cross-Over Studies Inhalation business.industry Nebulizers and Vaporizers Inhaler Biochemistry (medical) Dry Powder Inhalers Middle Aged medicine.disease Crossover study Fluticasone-Salmeterol Drug Combination Dry-powder inhaler Area Under Curve Female Salmeterol business medicine.drug |
| Zdroj: | Pulmonary Pharmacology & Therapeutics. 29:66-73 |
| ISSN: | 1094-5539 |
| Popis: | Aim To compare salmeterol (SALM) and fluticasone propionate (FP) systemic exposure following inhaled salmeterol/fluticasone propionate combination (SFC) from a unit-dose capsule-based inhaler (Rotacaps ® /Rotahaler ® ) and a multi-dose dry powder inhaler (Diskus ® ) in healthy volunteers. Methods An open-label, randomised, repeat-dose, cross-over, adaptive design study ( n = 36 in each part) evaluated SFC 50/250 μg and SFC 50/100 μg in Rotacaps used with two types of Rotahaler inhalers (airflow resistance similar to (S) and lower than (L) Diskus) versus the Diskus. Primary endpoints were area under the concentration-time curve over the dosing interval [AUC 0–τ ] and maximum plasma concentration [ C max ]. Results SFC 50/250 μg Rotacaps/Rotahaler (S) showed 1.2–1.9-fold greater FP and SALM systemic exposure compared with Diskus. FP and SALM systemic exposure were comparable to DISKUS following SFC 50/250 μg Rotacaps/Rotahaler (L) (90% CI of ratio of Rotahaler to DISKUS within 0.8–1.25) for salmeterol (AUC 0–τ and C max ) and FP (AUC 0–τ ). Following SFC 50/100 μg Rotacaps/Rotahaler (L), FP and SALM systemic exposures were 1.2–1.4 fold higher in terms of FP (AUC 0–τ and C max ) and salmeterol ( C max ) compared with Diskus. SFC at both doses and via both inhalers was well tolerated. Conclusions SFC 50/250 μg Rotacaps/Rotahaler (L) showed comparable systemic exposure to Diskus in terms of FP AUC and SALM AUC and C max . These results merit further progression of SFC 50/250 μg Rotacaps/Rotahaler (L) to phase 3 clinical evaluation in asthma and COPD patients. The lack of pharmacokinetic comparability between the inhalers for SFC 50/100 μg requires further evaluation. |
| Databáze: | OpenAIRE |
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