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ALPHA1-PROTEINASE INHIBITOR (A1PI) FUNCTIONAL AND ANTIGENIC LEVELS: EFFECT OF SUPPLEMENTATION. • 462

Objective: A1PI (Prolastin/Bayer) supplementation has been used in adults with emphysema associated with inherited A1-antitrypsin(A1AT) deficiency. A weekly infusion of 60 mg/kg produces normal antigenic values of 106-158 mg/dl and functional levels of 120-160 U inhibition/ml. The serum half life of the product is approximately 4.5 days. We attempted to determine the disposition of A1PI in premature infants who received 60 mg/kg on Days 0, 4, 7 and 14 in a trial for the prevention of bronchopulmonary dysplasia.

Method: As part of a randomized, placebo-controlled, double-blind trial, functional and antigenic serum levels of A1PI were measured on the first 23 patients on Days 0 (pre), 1, 2, 3, 4, 7, 10 and 14. The antigen levels were measured by electro-immunoassay with monospecific anti-human A1AT antibody. The functional levels were determined as an inhibitory activity of serum on human leukocyte elastase function.

Results: The antigenic level was 166.7 ± 46.2 (mean± S.D.) mg/dl and functional level 151.1 ± 52.4 U inhibition/ml prior to the first dose. On both assays, levels rose from Day 1 to 10 to maximums 275.1 ± 44.0 and 237.1 ± 23.6 respectively, then fell slightly, but remained above initial values. The levels were not significantly different between the treatment and placebo groups. As previously noted in our neonatal rat model (Ped Res 36:763, 1994), antigenic levels did not increase in a fashion similar to human adult studies.

Conclusion: Neonatal pharmacokinetics of A1PI differ markedly from the adult. Total plasma clearance of exogenous A1PI seems high in the premature neonate. Higher or more frequent doses may be necessary to maintain A1PI serum levels in premature infants higher than baseline. The link between the therapeutic effects and serum levels, as well as the route of clearance, needs further analysis. (Funding received from Bayer/Canadian Red Cross Society Research & Developmental Fund.)

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Stiskal, J., Ito, S., Cox, D. et al. ALPHA1-PROTEINASE INHIBITOR (A1PI) FUNCTIONAL AND ANTIGENIC LEVELS: EFFECT OF SUPPLEMENTATION. • 462. Pediatr Res 39, 79 (1996). https://doi.org/10.1203/00006450-199604001-00482

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