Functional and antigenic concentrations of alpha-1-proteinase inhibitor after administration for the prevention of chronic lung disease of prematurity

Objective and Methods: Alpha-1-proteinase inhibitor (A1PI) supplementation has been used in adults with inherited alpha-1-antitrypsin (A1AT) deficienc y to impede the development of emphysema. A1PI supplementation may also be useful for protecting premature neonates who receive mechanical ventilation from the development of chronic lung disease (CLD). However, the pharmacok inetics of exogenous A1PI in this population are unknown. We attempted to d etermine the disposition of A1PI in premature infants with birth weight 600 -1,250 g who received 60 mg/kg on days 0, 4, 7 and 14 in a randomized, plac ebo-controlled, double-blind trial. Functional and antigenic plasma concent rations of A1PI were measured at specified time points. Results: On both fu nctional and antigenic assays, concentrations began in the normal adult ran ge and rose from day 0 to 10 then fell slightly, but remained above initial values. The concentrations were not significantly different between the tr eatment and placebo groups. Conclusions: The results of this study indicate that neonatal pharmacokinetics of A1PI differ markedly from those of the a dult. Total plasma clearance of exogenous A1PI seems high in the ventilated premature neonate. Higher or more frequent doses may be necessary to maint ain A1PI plasma concentrations above baseline.