Pharmacokinetics in rabbits and anti-sphingomyelinase D neutralizing power of Fab, F(ab’)(2), IgG and IgG(T) fragments from hyper immune equine plasma.
Abstract: We describe the separation of whole IgG, IgG(T)-less IgG (called here merely IgG) and IgG(T) and the production of Fab and F(ab')(2) fragments. We studied the pharmacokinetics of these immunoglobulins and fragments in rabbits. Both, the isotypes and the whole IgG fragments were purified and/or produced from the same plasma lot from horses hyper immunized against sphingomyelinase D to produce anti-Loxosceles antivenom. The sphingomyelinase D neutralizing ability of the isotypes and their fragments was measured. Fab and F(ab')(2) PK was well described by a tri-exponential kinetics. IgG and IgG(T) PK, however, deviated from the tri-exponential kinetics 120h after injecting a bolus of the immunotherapeutics. The departure between tri-exponential PK and the experimental data, was shown to be due to a surge of anti-horse antibodies occurring after 120h, peaking at approximately 260h and decaying slowly afterward.
Copyright 2010. Published by Elsevier B.V.
Publication Date: 2010-01-20 PubMed ID: 20093203DOI: 10.1016/j.intimp.2010.01.005Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This study is about the extraction and analysis of different types of immunoglobulins and its fragments from the plasma of hyper immunized horses, their pharmacokinetic properties in rabbits and their neutralizing ability against sphingomyelinase D, an enzyme which forms part of the venom of Loxosceles spiders.
Process of Immunoglobulin Separation
- The study focused on the sequential processing and separation of different types of immunoglobulins from horse plasma. Specifically, these were whole IgG, IgG(T)-less IgG (referred to in this study as IgG) and IgG(T).
- The researchers also manufactured Fab and F(ab’)(2) fragments from these antibodies. Fab and F(ab’)(2) are smaller antibody pieces obtained by cleaving the full antibody molecule.
Pharmacokinetics in Rabbits
- Pharmacokinetics is the study of how a drug is absorbed, distributed, metabolized and eliminated by the body over time. Here, researchers studied the pharmacokinetics of the mentioned immunoglobulin types and fragments in rabbits.
- The Fab and F(ab’)(2) fragments demonstrated a tri-exponential pharmacokinetic model well, which is a pattern of absorption and elimination over time that can be described mathematically as the sum of three exponential functions.
- However, the pharmacokinetics of the IgG and IgG(T) immunoglobulins departed from the tri-exponential model 120 hours after the rabbits were injected with these immunotherapeutics, due to the rabbits producing anti-horse antibodies. This resulted in a surge of these anti-horse antibodies after about 120 hours, peaking at approximately 260 hours and slowly decreasing afterwards.
Anti-Sphingomyelinase D Neutralizing Power
- The horses from which the plasma was sourced were hyper immunized against sphingomyelinase D. This enzyme is present in the venom of the Loxosceles spider species, suggesting the primary use of these antibodies and fragments would be as an antivenom for Loxosceles spider bites.
- The researchers also studied the sphingomyelinase D neutralizing power of these immunoglobulins and their fragments. However, the abstract doesn’t provide in-depth findings on these results.
Cite This Article
APA
Vázquez H, Olvera F, Paniagua-Solís J, Alagón A, Sevcik C.
(2010).
Pharmacokinetics in rabbits and anti-sphingomyelinase D neutralizing power of Fab, F(ab’)(2), IgG and IgG(T) fragments from hyper immune equine plasma.
Int Immunopharmacol, 10(4), 447-454.
https://doi.org/10.1016/j.intimp.2010.01.005 Publication
Researcher Affiliations
- Laboratorios Silanes S.A. de C.V., Mexico City, México.
MeSH Terms
- Animals
- Antivenins / metabolism
- Antivenins / pharmacology
- Area Under Curve
- Chromatography, High Pressure Liquid
- Enzyme-Linked Immunosorbent Assay
- Horses / immunology
- Immune Sera / immunology
- Immunoglobulin Fab Fragments / metabolism
- Immunoglobulin Fab Fragments / pharmacology
- Immunoglobulin Fragments / metabolism
- Immunoglobulin Fragments / pharmacology
- Immunoglobulin G / metabolism
- Kinetics
- Phosphodiesterase Inhibitors / pharmacology
- Phosphoric Diester Hydrolases / immunology
- Phosphoric Diester Hydrolases / metabolism
- Rabbits
- Spider Venoms / immunology
Citations
This article has been cited 1 times.- Cui Z, Li D, Yi S, Guo Y, Dong G, Niu J, Zhao H, Zhang Y, Zhang S, Cao L, Wang K, Zhao Y, Hu G. Equine immunoglobulin F(ab')(2) fragments protect cats against feline calicivirus infection. Int Immunopharmacol 2019 Oct;75:105714.
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