Metabolism kinetics of beclomethasone propionate esters in human lung homogenates

Purpose. The purposes of this study were to characterize the kinetics of be clomethasone dipropionate (BDP) and its 17-monopropionate ester (17-BMP) in human lung 1000g supernatant (HLu) at 37 degrees C, and to analyze the int erindividual variability in the metabolism of BDP in HLu. Methods. The concentrations of BDP and its metabolites were determined by H PLC with UV detection at 242 nm. Kinetics of BDP and 17-BMP decomposition w ere characterized by least-squares fitting of rate equations. Results. The active metabolite 17-BMP was rapidly formed following the incu bation of BDP in HLu. Kinetics of BDP and 17-BMP in HLu were nonlinear owin g to product inhibition and enzyme saturation. A model taking into account the product inhibition provides a kinetic basis for understanding the in vi vo behavior of BDP and its metabolites in human lung. There was approximate ly a 3.5-fold difference in the initial half-life of BDP in HLu observed in seven subjects. Conclusions. An effective activation of BDP was demonstrated in HLu through the rapid formation of 17-BMP. Kinetics of BDP and 17-BMP in HLu were well characterized by the nonlinear kinetic model. Interindividual difference i n the initial half-life of BDP was due mainly to esterase metabolizing acti vity rather than binding affinity.