生物学的同等性とバイオアベイラビリティのジャーナル

概要

Comparison of Systemic and Pulmonary Bioavailability of Fluticasone Propionate HFA pMDI 250 Mcg per Actuation With and Without Spacer Device in Healthy Volunteers

Garg M, Naidu R, Birhade A, Iyer K, Jadhav R, Rebello J, Morde N and Brashier B

Fluticasone Propionate (FP) is a topically active corticosteroid which shows little or no systemic activity after oral administration and is indicated for the prophylactic management of asthma of all severities. The aim of these studies was to evaluate systemic exposure and pulmonary deposition of two Hydrofluoroalkane (HFA) formulations of fluticasone propionate with and without a spacer device in, healthy volunteers. Study-1 was a, randomized, single dose, laboratory-blinded, 2-sequence, 4-period, crossover replicate design without volumatic spacer in 32 healthy volunteers under fasting conditions. Study-2 was a randomized, single dose, laboratory-blinded, 2-sequence, 2-period, crossover design with volumatic spacer in 28 healthy volunteers under fasting conditions. A washout period of 14 days was included in both the studies. Blood samples were collected up to 36 h post-dose for pharmacokinetic profiling. Safety evaluations included assessment of vital signs, clinical laboratory parameters and monitoring of adverse events. A validated LC-MS/MS method was used to measure the plasma concentrations of fluticasone propionate. The 90% CI of the difference between the test (T) and reference (R) for fluticasone propionate was 97.46-112.34 and 98.55-113.06 for Cmax, and AUC0-t respectively in study-1. The 90% CI of the difference between the test and reference for fluticasone propionate was 88.13-104.88, and 96.21-111.22 for Cmax, and AUC0-t respectively in study-2. The 90% CI (T/R) for fluticasone propionate for both Cmax and AUC0-t was within the bioequivalence limits of 80-125% in both the studies. Hence, it was concluded that test and reference formulations of fluticasone propionate HFA pMDI 250 mcg per actuation are equivalent in the systemic exposure and pulmonary deposition with and without a spacer device.