Intravenous human plasma-derived augmentation therapy in alpha 1-antitrypsin deficiency: from pharmacokinetic analysis to individualizing therapy

The Annals of Pharmacotherapy
Nuria Padullés ZamoraJose Bruono Montoro Ronsano

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. He...Continue Reading

References

May 1, 1977·Clinical Science and Molecular Medicine·C B LaurellJ O Jeppsson
Aug 1, 1992·Clinical Pharmacokinetics·J ConstansC Tavera
Apr 23, 1987·The New England Journal of Medicine·M D WewersR G Crystal
Jun 25, 1998·Drugs & Aging·M Schwaiblmair, C Vogelmeier
Oct 3, 2003·American Journal of Respiratory and Critical Care Medicine·UNKNOWN American Thoracic Society, UNKNOWN European Respiratory Society
Oct 28, 2006·Archivos de bronconeumología·Rafael Vidal PlaJosé Bruno Montoro Ronsano

❮ Previous
Next ❯

Citations

Aug 27, 2009·Proceedings of the National Academy of Sciences of the United States of America·Mark L BrantlyTerence R Flotte
Jun 19, 2013·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Alice M Turner
Jan 14, 2011·Current Medical Research and Opinion·F Kueppers
Nov 7, 2013·Human Gene Therapy. Clinical Development·Maria J ChiuchioloRonald G Crystal
Jul 24, 2010·Therapeutic Advances in Respiratory Disease·Adriano R Tonelli, Mark L Brantly
Sep 26, 2019·Expert Opinion on Investigational Drugs·Anita Pye, Alice M Turner
Apr 26, 2014·Current Protocols in Human Genetics·Wylie Burke
Nov 1, 2011·Transfusion clinique et biologique : journal de la Société française de transfusion sanguine·O Erhabor, T C Adias

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Canadian Family Physician Médecin De Famille Canadien
Alan Kaplan, Lidia Cosentino
Canadian Respiratory Journal : Journal of the Canadian Thoracic Society
R T AbboudStnadards Committee of the Canadian Thoracic Society
© 2022 Meta ULC. All rights reserved