This study evaluated the bioavailability of a new preparation of alpha1-proteinase inhibitor (A1-PI), Zemaira® (ZLB Behring LLC, [Z(A1-PI)]), with that of Prolastin® (Bayer Corporation, [P(A1-PI)]) after single intravenous infusions.
This was a double-blind, randomized, controlled, 2x2 crossover study comparing a single dose of Z(A1-PI) and P(A1-PI) (60 mg per kg bodyweight). Patients with AATD were randomized (n=9 per group) to Z(A1-PI) followed by P(A1-PI), or P(A1-PI) followed by Z(A1-PI), with a washout period between infusions of 35 days. Bioavailability was measured by two baseline-adjusted area-under-the-curve (AUC) variables: area-under-the observed data up to Day 21 (AUD0-21) and AUD0-∞. The ratio of mean AUC variables (Z(A1-PI):P(A1-PI)) with 90% confidence intervals (CI) was calculated. Standard pharmacokinetic (PK) parameters Cmax, tmax, terminal t
, mean residence time, total clearance, and steady-state volume of distribution were also compared.
The bioavailability of Z(A1-PI) was statistically non-inferior to P(A1-PI) as shown by the lower limit of the 90% CI for the mean AUC ratio (Z(A1-PI):P(A1-PI)) being greater than 80% for AUD0-21 and also for AUD0-∞ (Table). Furthermore, the PK profile of functional A1-PI levels following Z(A1-PI) and P(A1-PI) administration showed no clinically relevant differences in terms of mean (SD) Cmax (39.9±5.3 vs. 41.6±8.0 μM), tmax (0.7±0.3 vs. 1.5±1.4 hours), terminal t
(4.5±3.1 vs. 4.8±1.2 days), mean residence time (5.9±3.3 vs. 6.1±1.3 days), total clearance (636±115 vs. 583±108 mL/day) or steady-state volume of distribution (3.6±1.3 vs. 3.5±0.8 L). The PK profile was reflected by that of antigenic A1-PI levels.
A single therapeutic dose of Z(A1-PI) was comparable and statistically not inferior to P(A1-PI) in bioavailability. There were no differences between Z(A1-PI) and P(A1-PI) in standard pharmacokinetic parameters.
Since Z(A1-PI) is statistically not inferior to P(A1-PI) in bioavailability, a weekly infusion of Z(A1-PI) 60 mg per kg body weight is expected to augment and maintain A1-PI serum levels above the protective threshold of 11 μM, and increase A1-PI levels in the lower lung, to a similar extent to that reported with P(A1-PI).
James Stocks, None.