Functional and antigenic concentrations of alpha-1-proteinase inhibitor after administration for the prevention of chronic lung disease of prematurity.
OBJECTIVE
Alpha-1-proteinase inhibitor (A1PI) supplementation has been used in adults with inherited alpha-1-antitrypsin (A1AT) deficiency 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 pharmacokinetics of exogenous A1PI in this population are unknown. We attempted to determine 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, placebo-controlled, double-blind trial. Functional and antigenic plasma concentrations of A1PI were measured at specified time points.


RESULTS
On both functional and antigenic assays, concentrations began in the normal adult range and rose from day 0 to 10 then fell slightly, but remained above initial values. The concentrations were not significantly different between the treatment and placebo groups.


CONCLUSIONS
The results of this study indicate that neonatal pharmacokinetics of A1PI differ markedly from those of the adult. Total plasma clearance of exogenous A1PI seems high in the ventilated premature neonate. Higher or more frequent doses may be necessary to maintain A1PI plasma concentrations above baseline.
Stiskal
J A
JA
Divisions of Clinical Pharmacology and Toxicology, Genetics, Neonatology, Cardiology, and The Research Institute, The Hospital for Sick Children, Toronto, Ont., Canada.
Ito
S
S
Cox
D W
DW
Shennan
A T
AT
O'Brien
K K
KK
Kelly
E N
EN
Longley
T B
TB
Rabinovitch
M
M
Dunn
M S
MS
D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D001997:Bronchopulmonary Dysplasia / Q000517:prevention & control*; D004311:Double-Blind Method; D005260:Female; D005322:Premature Rupture of Fetal Membranes; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D008297:Male; D010919:Placebos; D011247:Pregnancy; D011446:Prospective Studies; D000515:alpha 1-Antitrypsin / Q000032:analysis / Q000493:pharmacokinetics* / Q000627:therapeutic use*
D000305:Adrenal Cortex Hormones; D010919:Placebos; D000515:alpha 1-Antitrypsin