Comparative Kinetics of Metabolism of Beclomethasone Propionate Esters in Human Lung Homogenates and Plasma

The systemic availability of inhaled beclomethasone dipropionate (BDP) is the net result of the absorption of the glucocorticoid from the lower respiratory and gastrointestinal tracts, and metabolism in the lung, plasma, and other sites. The metabolism kinetics of BDP and its active metabolite, beclomethasone 17‐monopropionate (17‐BMP), in human lung 1000 × g supernatant (HLu) and human plasma (HP) at 37 °C were compared. The effect of MgCl2 and/or an NADPH‐generating system on the decomposition of BDP and 17‐BMP in HLu was also investigated. The concentrations of BDP and its metabolites were determined by HPLC with UV detection at 242 nm. Kinetics of decomposition of BDP and 17‐BMP in HLu and HP were qualitatively and quantitatively different. The decomposition of BDP in HLu involved only hydrolysis. In comparison, three reactions are involved following incubation of BDP in HP; namely, hydrolysis, transesterification, and loss of hydrogen chloride. The hydrolysis of BDP and 17‐BMP in HLu seem to be inhibited appreciably by MgCl2 with the NADPH‐generating system. Effective activation of BDP in HLu, in combination with transesterification of 17‐BMP in HP, might favor a high ratio of local antiinflammatory activity to systemic side effects following inhalation of BDP. © 2000 Wiley‐Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 89: 1143–1150, 2000