Pharmacokinetic study of alpha(1)-antitrypsin infusion in alpha(1)-antitrypsin deficiency

Objectives: To ascertain how long 120 mg/kg alpha(1)-antitrypsin concentrate (alpha(1)-AT-C), administered IV every 2 weeks, can maintain alpha(1)-antitrypsin (alpha(1)-AT) serum levels above 70 to 80 mg/dL. Secondary objectives were to summarize the nature, severity, and relationship of a plasma-derived alpha(1)-AT-C infusion to any side effects, Methods: This,vas an open-label uncontrolled pharmacokinetic study. alpha(1)-AT-C was administered IV every 2 weeks for 10 infusions in 23 patients with PIZ alpha(1)-AT deficiency. Serum alpha(1)-AT levels and neutralizing elastase activity were measured preinfusion, postinfusion, and at nadir. During two infusion periods, daily serum alpha(1)-AT and neutralizing elastase activities were measured on the seventh to 14th days. Five patients received BAL assays for alpha(1)-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 alpha 1-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 alpha(1)-AT levels above 80 mg/dL for all 14 days. The serum alpha(1)-AT and neutralizing elastase levels correlated suggesting functional activity. The BAL alpha(1)-AT and neutralizing elastase activities were low and did not correlate with serum levels. Conclusion: alpha(1)-AT-C at 120 mg/kg administered every 2 weeks did not maintain nadir serum alpha(1)-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.