Evaluation of tamoxifen as a therapy to augment alpha-1-antitrypsin concentrations in Z homozygous alpha-1-antitrypsin-deficient subjects.
Tamoxifen, an agent that binds to intracytoplasmic estrogen receptors, was evaluated as a possible means of increasing alpha-1-antitrypsin (alpha 1AT) synthesis and/or secretion and thus alpha 1AT serum levels in subjects with the homozygous form of alpha 1AT deficiency. Administration of tamoxifen (10 mg twice daily) to 30 Z homozygotes for a 30-day period was not associated with adverse reactions. However, although serum alpha 1AT levels increased significantly (p less than 0.03), the increase was minor (average pretreatment levels, 32 +/- 1 mg/dl; levels at 30 days of therapy, 35 +/- 1 mg/dl) and far below the "threshold" level of 80 mg/dl considered "protective" against an increased risk for emphysema. Thus, while the concept that increasing alpha 1AT synthesis and/or secretion is a rational goal for treating the Z homozygous form of alpha 1AT deficiency, tamoxifen will not be useful in this regard.
D000328:Adult; D004341:Drug Evaluation; D005260:Female; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D013629:Tamoxifen / Q000627:therapeutic use*; D000515:alpha 1-Antitrypsin / Q000378:metabolism; D019896:alpha 1-Antitrypsin Deficiency
D000515:alpha 1-Antitrypsin; D013629:Tamoxifen