Document Detail

Lack of effect of oral 4-phenylbutyrate on serum alpha-1-antitrypsin in patients with alpha-1-antitrypsin deficiency: a preliminary study.
MedLine Citation:
PMID:  15187777     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: In homozygotes with ZZ genotype alpha-1-antitrypsin (alpha1AT) deficiency, mutant alpha1ATZ protein (alpha1ATZ) accumulates in hepatocytes, rather than being secreted into the blood. Homozygous individuals experience emphysema as a result of reduced levels of circulating alpha1AT in the lung with which to inhibit connective tissue breakdown. Homozygotes may also experience liver disease from the accumulation of alpha1ATZ within hepatocytes, which causes liver damage. A previous study indicated that the compound 4-phenylbutyrate (4-PBA) mediated a significant increase in release of alpha1ATZ from cells in tissue culture and in a mouse model of alpha1AT deficiency. The authors hypothesized that 4-PBA could be used to treat both the liver and lung disease of humans with alpha1AT deficiency. METHODS: In this preliminary, open label study the authors evaluated the effect of 14 days of oral 4-PBA therapy on alpha1AT blood levels in 10 patients with alpha1AT deficiency. RESULTS: There was no significant increase in alpha1AT blood level associated with 4-PBA administration. Symptomatic and metabolic side effects were significant. CONCLUSION: 4-PBA did not increase alpha1AT blood levels in humans with alpha1AT deficiency in this preliminary trial.
Jeffrey H Teckman
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of pediatric gastroenterology and nutrition     Volume:  39     ISSN:  0277-2116     ISO Abbreviation:  J. Pediatr. Gastroenterol. Nutr.     Publication Date:  2004 Jul 
Date Detail:
Created Date:  2004-06-09     Completed Date:  2005-01-13     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8211545     Medline TA:  J Pediatr Gastroenterol Nutr     Country:  United States    
Other Details:
Languages:  eng     Pagination:  34-7     Citation Subset:  IM    
Department of Pediatrics, Washington University School of Medicine, St. Louis Children's Hospital, St. Louis, Missouri, USA.
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MeSH Terms
Administration, Oral
Child, Preschool
Dose-Response Relationship, Drug
Liver Diseases / drug therapy*,  etiology
Lung Diseases / drug therapy*,  etiology
Middle Aged
Phenylbutyrates / administration & dosage*,  adverse effects,  therapeutic use
alpha 1-Antitrypsin / drug effects,  metabolism*
alpha 1-Antitrypsin Deficiency / complications*,  drug therapy,  genetics
Grant Support
Reg. No./Substance:
0/Phenylbutyrates; 0/alpha 1-Antitrypsin; 1821-12-1/4-phenylbutyric acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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