Objective: Severe alpha(1)-Antitrypsin (AAT) deficiency (PiZZ) predisposes to the development of emphysema. Intravenous augmentation therapy with purified human AAT has been available since 1988. The dosage has varied from 60 mg/kg body weight once weekly to 250 mg/kg once monthly. We have found the dosage of 120 mg/kg every 2 weeks to be the most convenient for the patients. The treatment is very expensive. The objective of this investigation was to study whether tailored pharmacokinetic dosing of human AAT allows self-administration and reduces the total annual dose and cost of intravenous augmentation therapy.
Methods: Five PiZZ individuals receiving purified human AAT at a dose of 120 mg/kg every 2 weeks were included in the study. Three patients had a percutaneous and one patient had a subcutaneous intravenous injection port system. After a 4-week interruption of the treatment an ordinary dose of 120 mg/kg human AAT was infused. Plasma AAT levels were determined preinfusion, postinfusion, and once daily for 10-14 days. The pharmacokinetic parameters of exogenous AAT were calculated for each patient. Based on these, individual dosage schemes were designed by computer simulation. The patients were treated with the new dose twice weekly for 4 weeks, and plasma AAT was determined immediately before the last two infusions.
Results: At a dose of 1 or 2 g twice weekly the median annual consumption of human AAT was reduced from 286 to 156 g/patient. The trough plasma AAT level was maintained above 0.70 g/l, which is considered as protective. The three patients who had an implanted percutaneous venous port system learned to administer the treatment by themselves at home. The other two patients were treated at home by the district nurse.
Conclusions: The results of our study indicate that tailored pharmacokinetic dosing of human AAT reduces the total annual dose and cost of IV augmentation therapy. In addition, this dosing facilitates self-administration of AAT and allows treatment at home.