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• W2120757466 abstract "Severe forms of alpha(1)-antitrypsin (AAT) deficiency require augmentation therapy by intravenous administration of purified preparations of AAT concentrate. Although standard AAT treatment schedules are widely available, pharmacokinetic studies characterizing AAT serum decay are scarce, and data on the variability of individual patients are almost nonexistent.To establish individual AAT pharmacokinetics and develop a predictive model based on simple pharmacokinetic characterization that can be used to optimize individual AAT dosing regimens.Seven patients with severe hereditary AAT deficiency (PI(*)ZZ phenotype) with serum AAT levels less than 0.50 g/L initially received AAT 180 mg/kg every 3 weeks. At 7, 14, and 21 days after AAT administration, serum samples were taken for quantitative AAT analysis and further one-compartment pharmacokinetic analysis. Subsequently, patients were rescheduled (dose and dosing interval) according to their individual responses. The influence of baseline AAT level, age, sex, body weight, and commercial AAT preparation was evaluated.The mean +/- SD AAT pharmacokinetic profile was: volume of distribution 127.6 +/- 31.9 mL/kg, clearance 10.13 +/- 1.84 mL/kg/day, and half-life 8.7 +/- 1.0 days. Hence, the mean optimized final AAT dose was 123.1 mg/kg every 2 weeks (range 118.5-125.6). AAT concentrations differed by a mean (geometrical) value of 3.9% (range -4.2% to 6.7%) from the minimum desired AAT serum trough of 0.50 g/L. The impact of baseline AAT levels and commercial AAT preparation used was statistically significant (p = 0.033 and p = 0.035, respectively). Differences between estimated and actual values were slightly lower when baseline AAT levels were taken into consideration, with a mean value of 3.3% (range -4.2% to 6.1%).AAT augmentation therapy can be effectively individualized on a pharmacokinetic basis with a simple, easily executed method." @default.
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• W2120757466 date "2008-04-15" @default.
• W2120757466 modified "2023-10-18" @default.
• W2120757466 title "Intravenous Human Plasma-Derived Augmentation Therapy in α₁-Antitrypsin Deficiency: From Pharmacokinetic Analysis to Individualizing Therapy" @default.
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• W2120757466 doi "https://doi.org/10.1345/aph.1k505" @default.
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