Objectives: To ascertain how long 120 mg/kg alpha1-antitrypsin concentrate (α1-AT-C), administered IV every 2 weeks, can maintain α1-antitrypsin (α1-AT) serum levels above 70 to 80 mg/dL. Secondary objectives were to summarize the nature, severity, and relationship of a plasma-derived α1-AT-C infusion to any side effects.
Methods: This was an open-label uncontrolled pharmacokinetic study. α1-AT-C was administered IV every 2 weeks for 10 infusions in 23 patients with PIZ α1-AT deficiency. Serum α1-AT levels and neutralizing elastase activity were measured preinfusion, postinfusion, and at nadir. During two infusion periods, daily serum α1-AT and neutralizing elastase activities were measured on the seventh to 14th days. Five patients received BAL assays for α1-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 α1-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 α1-AT levels above 80 mg/dL for all 14 days. The serum α1-AT and neutralizing elastase levels correlated suggesting functional activity. The BAL α1-AT and neutralizing elastase activities were low and did not correlate with serum levels.
Conclusion: α1-AT-C at 120 mg/kg administered every 2 weeks did not maintain nadir serum α1-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.