Alpha-1-antitrypsin augmentation treatment: does one size fit all?
- Correspondence to:
Dr J Stolk
Department of Pulmonology, Leiden University Medical Center, P O Box 9600, 2300 RC Leiden, The Netherlands; j.stolk.long{at}lumc.nl
A new model for the individual pharmacokinetic assessment of patients requiring AAT augmentation therapy
Alpha-1-antitrypsin (AAT) is synthesised and secreted in the liver by hepatocytes. Individuals who inherit homozygous Z alleles of AAT have a serum deficiency (AATD) resulting from accumulation of aberrant polymerised AAT in the endoplasmic reticulum of hepatocytes.1 The most specific therapeutic approach for AATD is augmentation therapy—that is, intravenous administration of purified AAT which aims to raise serum levels above the protective threshold of 0.5 g/l (~11 µM) to protect against proteolytic destruction of alveoli and development of emphysema.2 Based on current understanding, and confirmed by the American Food and Drug Administration CBER Blood Products Advisory Committee in 1998, the risk of emphysema increases as the serum level of AAT falls below a …
