alexa [Pharmacokinetics of alpha1-antitrypsin replacement therapy in severe congenital emphysema].

Kidney Disorders and Clinical Practices

Author(s): Vidal Pla R, Padulls Zamora N, Sala Piol F, Jard Margaleff R, Rodrguez Fras F,

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Abstract OBJECTIVE: Alpha1-antitrypsin (AAT) deficiency is a codominant autosomal genetic disorder that predisposes a patient to chronic obstructive pulmonary disease and emphysema. Specific treatment is systemic, consisting of intravenous infusion of AAT. The protocol currently recommended by the Spanish Registry is infusion of 180 mg/kg every 21 days. The objective of this study was to assess the pharmacokinetic behavior of AAT and estimate the level of protection, defined as the percentage of time that the AAT plasma concentration was above the assumed protective threshold of 50 mg/dL with the usual protocol and with other alternative ones. MATERIAL AND METHODS: Plasma concentrations at 4 times were analyzed for 9 patients to profile the pharmacokinetics of AAT. The data were fitted to a single compartment open model with the WinNonlin software package. The duration of protection was estimated by simulating the evolution of AAT plasma activity over time according to the model constructed based on data recorded in the study. RESULTS: Five men and 4 women (mean weight, 69 kg; range, 59-84 kg) were given a mean AAT dose of 12.06 g (range, 11-15 g). The mean (SD) volume infused was 516.67 (88.17) mL. The half-life of AAT was 8.7 days and the volume of distribution was 127.6 mL/kg. The currently recommended treatment protocol (180 mg/kg every 21 days) gave a level of protection of 67\% (considering 60 mg/dL to be protective threshold) or 76\% (for a threshold of 50 mg/dL). Protection values for the alternative protocol of 120 mg/kg every 14 days were 82\% and 100\%, respectively. For the alternative protocol of 60 mg/kg every 7 days, protection was 100\% for both thresholds. CONCLUSIONS: Profiling the pharmacokinetic behavior of AAT has enabled the coverage time to be assessed for several treatment protocols. The regimen of 120 mg/kg every 14 days had the most appropriate profile.
This article was published in Arch Bronconeumol and referenced in Kidney Disorders and Clinical Practices

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