Zeitschrift für Bioäquivalenz und Bioverfügbarkeit

Abstrakt

Bioequivalence of Two Formulations of Salmeterol Xinafoate/Fluticasone Propionate HFA pMDI in Healthy Volunteers

Muneesh Garg, Raghu Naidu, Amolkumar Birhade, Krishnan Iyer, Ratnakar Jadhav, Juliet Rebello, Nazma Morde, Mayuri Mangale and Bill Brashier

In the treatment of asthma, salmeterol xinafoate and fluticasone propionate are known to be effective and well accepted. These studies determined the bioequivalence between the test and reference formulations of salmeterol xinafoate/fluticasone propionate HFA pMDI, in healthy volunteers. Four pharmacokinetic studies were executed with two high strength (25/250 mcg per actuation) and two low strength (25/125 mcg per actuation) for the test and reference formulation. Mostly, the evaluation was based on single dose, randomized, crossover with a minimum washout period of 14 days. Out of the four studies (two for each strength) two also evaluated as pulmonary deposition by blocking gastrointestinal absorption using charcoal administration. Examinations for safety included monitoring of adverse events and vital signs along with clinical laboratory assessments. A validated LC-MS/MS technique was used to determine the plasma concentrations of salmeterol xinafoate and fluticasone propionate. In the research without charcoal blockade for salmeterol, the 90% CI for Cmax and AUC0-t for 25/250 mcg was 83.44-100.29 and 104.08-120.08 respectively, while for 25/125 mcg it was 88.33-106.08 and 100.49-114.88 respectively. Similarly, in the studies with charcoal blockade for salmeterol, the 90% CI for Cmax and AUC0-t for 25/250 mcg was 94.10- 113.20 and 96.44-116.69 respectively, while for 25/125 mcg it was 100.70-115.72 and 104.99-122.70 respectively. For fluticasone, the 90% CI for Cmax and AUC0-t for 25/250 mcg was 91.08-105.07 and 99.86-115.61 respectively and for 25/125 mcg, it was 87.04-105.03 and 85.38-103.42 respectively. Since the 90% CI for Cmax and AUC0-t for both salmeterol and fluticasone were within the 80-125% interval in all the studies, it was concluded that test and reference formulations of salmeterol xinafoate/fluticasone propionate HFA pMDI are bioequivalent in their rate and extent of absorption with and without charcoal blockade for both the strengths.