Fab Antibody Fragments

@article{Flanagan2004FabAF,
  title={Fab Antibody Fragments},
  author={R. J. Flanagan and Alison L Jones},
  journal={Drug Safety},
  year={2004},
  volume={27},
  pages={1115-1133}
}
This review provides current information on the use of antigen-binding fragments (Fab) from cleaved antibodies to treat poisoning with digoxin and other potent, low formula mass poisons, such as colchicine and tricyclic antidepressants. Anti-digoxin Fab fragments have been used successfully for many years in the management of severe poisoning with digoxin, digitoxin, and a range of other structurally related compounds, including cardiotoxins from Nerium and Thevetia sp. (oleander) and Bufo sp… 
Digoxin-specific antibody fragments in the treatment of digoxin toxicity
TLDR
Digoxin-Fab was used more frequently in acute than chronic digoxin poisoning with a higher reported success rate when used in acute overdose and full neutralisation doses may still be calculated because of variation in Vd due to equations failing to account for lean body weight, age and renal failure.
Digoxin-Specific Antibody Fragments
TLDR
An approach to therapy is proposed, which is based on theoretical principles and evidence gleaned from currently available clinical data sets, and suggests that half the calculated loading dose, based on serum concentration, should be administered and the impact on clinical features observed; a second dose should be given in the event of recurrence of toxicity.
Anti-Digoxin Fab Variants Generated by Phage Display
TLDR
This study is based on a monoclonal anti-digoxin antibody, which would provide a product with a specific potency and more precise dosage for the detoxification of patients under digoxin treatment.
DIGOXIN-SPECIFIC ANTIBODY FRAGMENTS
TLDR
The antibodies that were developed have a high affinity for digoxin, and sufficient cross-reactivity with digitoxin and other cardioactive steroids to be clinically useful for the treatment of all cardioactive steroid poisonings.
Physiologically based pharmacokinetic modelling of acute digoxin toxicity and the effect of digoxin-specific antibody fragments
TLDR
Compared to conventional two-compartment modelling, PBPK modelling is superior in generating realistic simulations of acute digoxin toxicity and the response to digoxin-Fab, providing realistic, continuous data which has the potential to substantiate alternative, less expensive, and safer dig toxin-Fab dosing strategies.
Therapeutic Drug Monitoring of Digoxin
TLDR
Clinicians should be aware of limitations of therapeutic drug monitoring of digoxin using immunoassays and monitor unbound (free) digoxin concentration under certain circumstances to eliminate such interferences.
Fab fragments of ovine antibody to colchicine enhance its clearance in the rat
TLDR
Clinical utility for Fab anti-colchicine in the treatment of colchicines overdose is suggested, although increasing NGAL level suggested the presence of mild kidney damage.
Extending the half-life of a fab fragment through generation of a humanized anti-human serum albumin Fv domain: An investigation into the correlation between affinity and serum half-life
TLDR
An anti-albumin antibody is generated to link its Fv domain to an antigen-binding fragment (Fab), thereby extending the serum half-life of the Fab and it is shown that CA645 Fab binds to domain II of HSA, and does not block HSA binding to neonatal Fc receptor (FcRn).
Mechanisms, Manifestations, and Management of Digoxin Toxicity in the Modern Era
Because of the common use of digoxin and because of its narrow therapeutic index, digoxin toxicity has been prevalent historically and, therefore, most clinicians are well aware of the classical
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References

SHOWING 1-10 OF 119 REFERENCES
Monitoring of unbound digoxin in patients treated with anti-digoxin antigen-binding fragments: a model for the future?
TLDR
The rationale for using Fab fragments to reduce toxic effects of digoxin is their greater affinity for digoxin when compared with the sodium pump, which is 10-fold lower than that of Digoxin; however, it is high enough to allow clinical utility of Fab fragments in cases of digitoxin intoxication as well.
Effects of sheep digoxin-specific antibodies and their Fab fragments on digoxin pharmacokinetics in dogs.
TLDR
Differences in urinary excretion, together with the probable decreased immunogenicity of sheep antidigoxin Fab fragments, suggest that such fragments possess potential advantages over intact antibody molecules for use in the therapy of life-threatening digoxin intoxication in man.
Kinetics of the fab fragments of digoxin antibodies and of bound digoxin in patients with severe digoxin intoxication
TLDR
17 patients with severe digoxin intoxication were successfully treated with 320 to 480 mg Fab fragments of digoxin-specific IgG from sheep, finding that the dosage of the antibody should be sufficiently high to bind digoxin in the most severe cases of poisoning.
Experience with digoxin immune Fab (ovine) in patients with renal impairment.
  • T. Wenger
  • Medicine, Biology
    The American journal of emergency medicine
  • 1991
Plasma exchange for the removal of digoxin-specific antibody fragments in renal failure: timing is important for maximizing clearance.
  • M. Zdunek, A. Mitra, M. Mokrzycki
  • Medicine, Biology
    American journal of kidney diseases : the official journal of the National Kidney Foundation
  • 2000
TLDR
It is concluded that the optimal timing of PE is within the first 3 hours after Fab administration, which is not efficacious for improving total digoxin clearance because of the large apparent volume of distribution of digoxin.
Digoxin Poisoning and Anuric Acute Renal Failure: Efficiency of the Treatment Associating Digoxin-Specific Antibodies (Fab) and Plasma Exchanges
TLDR
The disappearance of cardiac abnormalities showed the efficiency of the Fab, the drop in serumdigoxin concentration and the high digoxin concentration in the exchanged plasma indicate effective elimination, and the association of Fab and plasma exchanges could be proposed in the case of digoxin intoxication in the anuric patient.
Review of clinical experience with digoxin immune Fab (ovine).
  • T. Smith
  • Medicine
    The American journal of emergency medicine
  • 1991
Development of a Sensitive Radioimmunoassay for Fab Fragments: Application to Fab Pharmacokinetics in Humans
TLDR
Anti-sheep Fab fragment antisera were produced in rabbits using sheep digoxin-specific Fab fragments (Digidot) as immunogen for the development of a radioimmunoassay (RIA) of sheep Fab fragments in human plasma and urine using 125I-labeled Fab fragments.
Disposition of a monoclonal anti-phencyclidine Fab fragment of immunoglobulin G in rats.
TLDR
The pharmacokinetics of an anti-PCP monoclonal antibody Fab (antigen binding fragment of immunoglobulin G) were determined in adult male Sprague-Dawley rats and all animals tolerated the Fab infusion without adverse effect.
Digoxin Measurements following Plasma Ultrafiltration in Two Patients with Digoxin Toxicity Treated with Specific Fab Fragments
TLDR
Two further cases of digoxin intoxication are presented in which Fab fragments were used in therapy, and free digoxin concentrations were measured in plasma ultrafiltrate.
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