Population Pharmacokinetics Of Inhaled Fluticasone Furoate And Vilanterol In Adult And Adolescent Patients With Asthma

Objectives: Population pharmacokinetic (PK) methods were used to characterize the PK of fluticasone furoate (FF) and vilanterol (VI) in patients with asthma following once daily inhaled FF/VI and FF and to identify significant covariates that impact the PK. Materials and methods: Four of the five studies in the meta-analysis were conducted in patients with asthma (> 90%), the fifth in healthy subjects. FF data were described by a two-compartment model with first order absorption and elimination. VI data were described by a three-compartment model with zero-order absorption and first order elimination. Results: Race was a significant covariate on inhaled clearance (CL/F) of FF PK. AUC((0-24))) for Asian patients was on average 33 - 53%. higher than for non-Asians. Race was also a significant covariate on VI PK, with lower (81%) central volume of distribution (Vc/F) for Asian patients compared with non-Asians; VI C-max was 220 - 287% higher in Asian patients. Treatment (combination or monotherapy), predicted percentage FEV1, and other demographic variables did not influence the PK of FF or VI. Conclusions: Combination of FF/VI does not appear to affect the PK of FF or VI. The effect of race on PK of FF or VI does not have impact on dosage adjustments for FF/VI in East Asian patients with asthma.