The pharmacokinetics, safety, and tolerability of single, high-strength doses of fluticasone propionate and fluticasone propionate/salmeterol delivered via a novel multidose dry powder inhaler in adolescents and adults with persistent asthma.
J Asthma
; 55(8): 898-906, 2018 08.
Article
em En
| MEDLINE
| ID: mdl-28933971
ABSTRACT
OBJECTIVE:
Characterize fluticasone propionate (Fp) and combination fluticasone propionate and salmeterol (FS) pharmacokinetic and safety profiles, delivered via a novel, inhalation-driven, multidose dry powder inhaler (MDPI).METHODS:
This multicenter, open-label, four-period crossover, single-dose study randomized patients aged ≥12 years with persistent asthma to Fp MDPI 200 mcg, FS MDPI 200/12.5 mcg, Fp dry powder inhaler (DPI) 500 mcg (250 mcg × 2 inhalations), or FS DPI 500/50 mcg. Blood samples for determination of Fp and salmeterol pharmacokinetic parameters including Cmax, AUC0-t, AUC0-inf, tmax, and t½ were collected predose through 36 h postdose (14 time points). Safety assessments comprised adverse events, vital signs, and physical examinations. The institutional review board approved the study protocol.RESULTS:
The pharmacokinetic analysis set and safety population each included 40 patients. Fp systemic exposure (Cmax, AUC0-t, and AUC0-inf) was highest for Fp DPI 500 mcg and similar for Fp MDPI 200 mcg, FS MDPI 200/12.5 mcg, and FS DPI 500/50 mcg. Fp geometric mean t½ values were similar across treatments. Salmeterol Cmax was 20% lower and AUC0-t and AUC0-inf were approximately 50% lower with FS MDPI versus FS DPI. Median tmax and geometric mean t½ were similar between FS MDPI and FS DPI. Adverse events were similar across treatments with no relevant changes in vital signs, physical examinations, or hematology test results.CONCLUSIONS:
Fp MDPI and FS MDPI produced similar or lower systemic exposure to Fp and salmeterol, despite lower doses, versus conventional DPI devices, suggesting improved efficiency due to formulation and device differences.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Asma
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Broncodilatadores
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Combinação Fluticasona-Salmeterol
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Fluticasona
Tipo de estudo:
Clinical_trials
/
Guideline
/
Prognostic_studies
Limite:
Adolescent
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Adult
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Aged
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Child
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Asthma
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos