Pharmacokinetic study of alpha1-antitrypsin infusion in alpha1-antitrypsin deficiency.
OBJECTIVE
To ascertain how long 120 mg/kg alpha1-antitrypsin concentrate (alpha1-AT-C), administered I.V. every 2 weeks, can maintain alpha1-antitrypsin (alpha1-AT) serum levels above 70 to 80 mg/dL. Secondary objectives were to summarize the nature, severity, and relationship of a plasma-derived alpha1-AT-C infusion to any side effects.


METHODS
This was an open-label uncontrolled pharmacokinetic study. Alpha1-AT-C was administered I.V. every 2 weeks for 10 infusions in 23 patients with PIZ alpha1-AT deficiency. Serum alpha1-AT levels and neutralizing elastase activity were measured preinfusion, postinfusion, and at nadir. During two infusion periods, daily serum alpha1-AT and neutralizing elastase activities were measured on the seventh to 14th days. Five patients received BAL assays for alpha1-AT and neutralizing elastase activity. Adverse events were recorded in a patient diary and by a nurse at each infusion visit.


RESULTS
The 120-mg/kg dose of alpha1-AT-C could not maintain nadir serum protective levels above 70 or 80 mg/dL for the entire 14-day dosing interval in most patients. None of the patients had alpha1-AT levels above 80 mg/dL for all 14 days. The serum alpha1-AT and neutralizing elastase levels correlated suggesting functional activity. The BAL alpha1-AT and neutralizing elastase activities were low and did not correlate with serum levels.


CONCLUSIONS
Alpha1-AT-C at 120 mg/kg administered every 2 weeks did not maintain nadir serum alpha1-AT levels above 70 to 80 mg/dL for a 14-day dosing interval. Higher doses every 2 weeks or decreased interval between infusions may be required.
Barker
A F
AF
Department of Medicine, Oregon Health Sciences University, Portland, USA.
Iwata-Morgan
I
I
Oveson
L
L
Roussel
R
R
D000328:Adult; D000368:Aged; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D003371:Cough / Q000139:chemically induced; D004334:Drug Administration Schedule; D004417:Dyspnea / Q000139:chemically induced; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006261:Headache / Q000139:chemically induced; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008499:Medical Records; D008875:Middle Aged; D010196:Pancreatic Elastase / Q000097:blood; D012220:Rhinitis / Q000139:chemically induced; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000172:deficiency / Q000493:pharmacokinetics*; D016896:Treatment Outcome; D014361:Trypsin Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000172:deficiency / Q000493:pharmacokinetics*; D014797:Vital Capacity / Q000187:drug effects; D000515:alpha 1-Antitrypsin / Q000008:administration & dosage / Q000009:adverse effects / Q000032:analysis / Q000493:pharmacokinetics*
D015842:Serine Proteinase Inhibitors; D014361:Trypsin Inhibitors; D000515:alpha 1-Antitrypsin; D010196:Pancreatic Elastase