Pediatric Constipation Therapy Using Guidelines and Polyethylene Glycol 3350

Bell, Edward; Wall, Geoffrey C.

doi:10.1345/aph.1d297

Cited by 23 publications

(15 citation statements)

References 22 publications

(26 reference statements)

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“…Pre-existing antibodies to polyethylene glycol (PEG) are reported in various frequencies dependent on the level of prior exposure to PEG-containing commodities or medical procedures, as well as the analytical methods used for pre-existing antibody detection (16,(36)(37)(38)(39). While a high prevalence of anti-PEG preexisting antibodies was not associated with impaired response to PEG-interferon in hepatitis C patients, increased drug clearance, reduced efficacy, and increased infusion reactions have been reported for pegloticase (PEG-porcine uricase) in patients with refractory chronic gout (14,40).…”

Section: Pre-existing Antibodies To Pegylated Drugsmentioning

confidence: 99%

Recommendations for the Assessment and Management of Pre-existing Drug-Reactive Antibodies During Biotherapeutic Development

Xue

Clements-Egan

Amaravadi

et al. 2017

AAPS J

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Abstract.Anti-drug antibodies (ADA) pose a potential risk to patient safety and efficacy and are routinely monitored during clinical trials. Pre-existing drug-reactive antibodies are present in patients without prior drug exposure and are defined by their ability to bind to a component of the drug. These pre-existing drug-reactive antibodies are frequently observed and could represent an adaptive immune response of an individual who has been previously exposed to antigens with structural similarities to the biotherapeutic. Clinical consequences of these antibodies can vary from no impact to adverse effects on patient safety, exposure, and efficacy, and are highly dependent on biotherapeutic modality, disease indications, and patient demographics. This paper describes how the immunogenicity risk assessment of a biotherapeutic integrates the existence of pre-existing drug-reactive antibodies, and provides recommendations for risk-based strategies to evaluate treatment-emergent ADA responses.

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Section: Pre-existing Antibodies To Pegylated Drugsmentioning

confidence: 99%

Recommendations for the Assessment and Management of Pre-existing Drug-Reactive Antibodies During Biotherapeutic Development

Xue

Clements-Egan

Amaravadi

et al. 2017

AAPS J

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“…These studies are very difficult to conduct on the PEGylated material, and this leaves a possible concern about the PEGylated portion of the molecule and its impact on human safety. In their nonconjugated form, polyethylene glycols are widely used as excipients for a large variety of drugs and are also regularly used in children for the treatment of pediatric constipation or for colonoscopy (Pashankar et al, 2003(Pashankar et al, , 2004Bell and Wall, 2004).…”

mentioning

confidence: 99%

PEGylated Proteins: Evaluation of Their Safety in the Absence of Definitive Metabolism Studies

Webster

Didier²,

Harris³

et al. 2006

Drug Metab Dispos

312

281

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ABSTRACT:During the development of any PEGylated protein or peptide, toxicology in relevant species will be conducted prior to human exposure. Normally, comprehensive metabolism data accompany the toxicity studies for a small molecule. We have examined whether such studies would be relevant in the safety assessment of PEGylated material. Literature data indicate that the polyethylene glycol (PEG) associated with a biological molecule should provide no extra concern because the exposure-toxicity relationship of PEG in animals and humans has been thoroughly investigated and metabolism/excretion of PEG is well understood. Based on the comparisons of PEG exposure from PEGylated biological products and the exposure of PEG associated with toxicity in humans, the therapeutic index is large (approximately 600-fold or greater). Therefore, assuming that toxicological evaluation of a biological molecule of interest is complete and satisfactory therapeutic windows are achieved, the data contained in this review indicate that the PEG associated with a protein or other biological molecule does not represent an additional unquantified risk to humans.The conjugation of small proteins, peptides, and oligonucleotides with polyethylene glycol (PEG), or PEGylation, has become an increasingly common method of improving the half-life of biological products, mainly through reducing the urinary excretion of the molecule (Yang et al., 2004), but also by reducing the enzymic degradation due to the increased steric bulk (Veronese and Pasut, 2005). In addition, PEGylated biological products often exhibit a reduced affinity for the target receptor compared with the native precursor. This reduced affinity can lead to a lower clearance by target-mediated clearance mechanisms. Finally, the addition of the PEG moiety can have beneficial effects on the immunological profile of a molecule by reducing the ability of the compound to raise antibodies in humans (Mehvar, 2000).PEG is a polymer made up of identical ethylene glycol subunits. PEGs have a descriptor associated with them that represents the mean molecular weight of the molecule (i.e., PEG200 has a molecular weight of 200) (Smyth et al., 1955). The PEG molecules conjugated to proteins can also have the terminal hydroxyl group capped with a methyl group (Molineux, 2003). The structures of these PEGs are detailed in Fig. 1. Higher molecular weight PEGs can have some degree of branching. The PEGs used to conjugate biologicals are polydispersed in nature (i.e., have a range of molecular weights), and this can to lead to a range of drug molecules with potentially subtly different biological properties. The impact of polydispersity must be considered when dealing with these conjugated biological agents (Veronese and Pasut, 2005).To couple the PEG to the protein, peptide, or oligonucleotide, the PEG (generally monomethoxy PEG) is first activated. Several methods can be used to achieve this activation and coupling, including cyanuric chloride, 1,1Ј-carbonyldiimidazole, phenylchloroformate, or succi...

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Section: Discussionmentioning

confidence: 99%

“…Recently, Polyethylene glycols have received a great deal of attention due to effectiveness, palatability and safety and they were also recommended for subjects who have failed or are intolerant to other medications [7,9]. Different doses, durations, and success rates were used depending on study protocols [9][10][11][12][13][14][15]. Although PEG has been suggested with a dose of 0.2 -1.5 gr/Kg/day, the starting dose of 1 gr/Kg/day with adjustment every 3 days was recommended by Rahhal et al [1,5,[11][12][13][14][15].…”

Section: Discussionmentioning

confidence: 99%

A Comparative Trial: The Safety and Clinical Efficacy of PEG 3350 and Liquid Paraffin in Management of Chronic Functional Constipation in Children

Abbaslou¹,

Farzaneh²,

Ali³

2012

IJCM

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Background: Constipation is one of the most common problems in the pediatric age group. In the vast majority, chronic constipation is idiopathic or functional. In addition to education and behavioral changes, disimpaction and maintenance treatment with medications are the main pillars of successful outcome. The medications are variably effective and have potential side effects. Objectives: The current clinical trial was designed to evaluate clinical efficacy of polyethylene glycol (PEG) 3350 and liquid paraffin in chronic functional constipation. Besides, subjects were followed carefully for the side effects. Material and Methods: This study was involved 110 children suffering from chronic functional constipation. They were placed into two different groups, randomly. Each group was treated with PEG 3350 or liquid paraffin. The clinical efficacy and side effects were monitored. Results: After disimpaction with bisacodyl suppositories or combined with Mineral oil enemas in hard fecal impaction, maintenance therapy with PEG 3350 or liquid paraffin was started. The treatment duration and efficacies were not different between the two groups. Furthermore, serious adverse drug reaction was not observed. The family history of constipation and presence of incontinence were two worse prognostic factors. Conclusion: No difference was observed between PEG 3350 and liquid paraffin in chronic functional constipation in children in terms of their efficacies. They are safe and effective medications in this age group.

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Pediatric Constipation Therapy Using Guidelines and Polyethylene Glycol 3350

Abstract: PEG 3350 is an effective and well-tolerated treatment choice for pediatric constipation, especially as an adjunct to education and behavioral training. PEG 3350 is an option for children with constipation who have failed or are intolerant of other pharmacotherapies.

Cited by 23 publications

References 22 publications

Recommendations for the Assessment and Management of Pre-existing Drug-Reactive Antibodies During Biotherapeutic Development

Recommendations for the Assessment and Management of Pre-existing Drug-Reactive Antibodies During Biotherapeutic Development

PEGylated Proteins: Evaluation of Their Safety in the Absence of Definitive Metabolism Studies

A Comparative Trial: The Safety and Clinical Efficacy of PEG 3350 and Liquid Paraffin in Management of Chronic Functional Constipation in Children

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