Deposition and pharmacokinetics of an HFA formulation of triamcinolone acetonide delivered by pressurized metered dose inhaler

Novel formulations of asthma drugs contained in pressurized metered dose in halers (pMDls) are being developed containing hydrofluoroalkane (HFA) prope llants. The objectives of this study were to assess the deposition in the l ungs and oropharynx of triamcinolone acetonide (TAA; Azmacort((R)), Aventis Pharma, Collegeville, PA) delivered by pMDI formulated with HFA-134a, toge ther with the pharmacokinetic profile of TAA, and to determine the extent t o which the Azmacort((R)) spacer improves targeting of TAA to the lungs. Th e deposition of TAA, labelled with Tc-99m, was assessed by gamma scintigrap hy in 10 patients with mild to moderate asthma (mean forced expiratory volu me in one second [FEV1] 76% predicted), who received in randomized order th ree delivered (ex-device) doses of 75 mug TAA via pMDI coupled to an Azmaco rt((R)) spacer (TAA-spacer), and three delivered doses of 230 mug TAA via t he same device but with the spacer removed (TAA-no spacer). Mean lung depos ition expressed as mass of drug was similar for each regimen (TAA-no spacer 175 mug; TAA-spacer 188 mug), but when expressed as percentage delivered d ose, lung deposition was higher for TAA-spacer (53.8%) versus TAA-no spacer (26.0%), indicating superior drug targeting for TAA-spacer. The spacer red uced oropharyngeal deposition. The pharmacokinetic data showed higher plasm a levels of drug for TAA-no spacer, resulting from higher oropharyngeal dep osition. "'Pharmacoscintigraphic" data showed proof of concept for a novel HFA delivery system for an inhaled corticosteroid based on pulmonary target ing of drug.