SciCombinator

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Concept: Polyethylene glycol

168

BACKGROUND: PEG-based laxatives are considered today the gold standard for the treatment of constipation in children. PEG formulations differ in terms of composition of inactive ingredients which may have an impact on acceptance, compliance and adherence to treatment. We therefore compared the efficacy, tolerability, acceptance and compliance of a new PEG-only formulation compared to a reference PEG-electrolyte (PEG-EL) formulation in resolving faecal impaction and in the treatment of chronic constipation. METHODS: Children aged 2–16 years with functional chronic constipation for at least 2 months were randomized to receive PEG-only 0.7 g/kg/day in 2 divided doses or 6.9 g PEG-EL 1–4 sachets according to age for 4 weeks. Children with faecal impaction were randomized to receive PEG-only 1.5/g/kg in 2 divided doses until resolution or for 6 days or PEG-EL with an initial dose of 4 sachets and increasing 2 sachets a day until resolution or for 7 days. RESULTS: Ninety-six children were randomized into the study. Five patients withdrew consent before starting treatment. Three children discontinued treatment for refusal due to bad taste of the product (1 PEG-only, 2 PEG-EL); 1 (PEG-EL) for an adverse effect (abdominal pain). Intent-to-treat analysis was carried out in 49 children in the PEG-only group and 42 in the PEG-EL group.No significant differences were observed between the two treatment groups at baseline.Adequate relief of constipation in terms of normalized frequency and painless defecation of soft stools was achieved in all patients in both groups. The number of stools/week was 9.2 +/- 3.2 (mean +/- SD) in the PEG-only group and 7.8 +/- 2.4 in the PEG-EL group (p = 0.025); the number of days with stool was 22.4 +/- 5.1 in the PEG-only group and 19.6 +/- 7.2 in the PEG-EL group (p = 0.034).In the PEG-only group faecaloma resolution was observed in 5 children on the second day and in 2 children on the third day, while in the PEG-EL group it was observed in 2 children on the second day, in 3 children on the third day and in 1 child on the fifth day.Only 2 patients reported mild treatment-related adverse events: 1 child in the PEG-only group had diarrhoea and vomiting and 1 child in the PEG-EL group had abdominal pain requiring treatment discontinuation. The PEG-only preparation was better tolerated as shown by the lower frequency of nausea than in the PEG-EL group.In the PEG-only group, 96% of patients did not demonstrate any difficulties associated with treatment, as compared with 52% of patients in the PEG-EL group (p < 0.001). Also, the PEG-only formulation taste was better than that of PEG-EL (p < 0.001). The difference between the percentage of subjects who took > 80% of the prescribed dose was in favour of the PEG-only group (98% vs. 88%), though it did not reach a conventional statistical level (p = 0.062). CONCLUSION: PEG-only was better tolerated and accepted than PEG-EL in children with chronic constipation. At the higher PEG doses recommended by the manufactures children in the PEG-only group had higher and more regular soft stool frequency than PEG-EL.Trial registrationClinicalTrials.gov: NCT01592734.

Concepts: Randomized controlled trial, Constipation, Gastroenterology, Irritable bowel syndrome, Feces, Polyethylene glycol, Fecal impaction, Enema

164

To assess the renal safety of treatment with polyethylene glycol 3350 with electrolytes at 1, 3 and 6 months, its gastrointestinal tolerance and dose effectiveness.

Concepts: Constipation, Ether, Polyethylene glycol, Laxative

29

Subcutaneous pegylated interferon (peginterferon) beta-1a is being developed for treatment of relapsing multiple sclerosis, with less frequent dosing than currently available first-line injectable treatments. We assessed the safety and efficacy of peginterferon beta-1a after 48 weeks of treatment in the placebo-controlled phase of the ADVANCE trial, a study of patients with relapsing-remitting multiple sclerosis.

Concepts: Pharmacology, Interferon, Multiple sclerosis, Hepatitis B, Polyethylene glycol, Interferon beta-1a, Interferon beta-1b, Treatment of multiple sclerosis

2

We present three cases with anaphylaxis after injection of a depot corticosteroid. First, the steroid was suspected as the elicitor, but after evaluation the excipient macrogol was found to be the elicitor. One of the patients had reactions to several unrelated drugs. Increased awareness of anaphylaxis to excipients such as macrogols is needed, especially when allergy tests for the active drug is negative and in patients with a history of repeated anaphylaxis to seemingly unrelated drugs. To establish the correct diagnosis it is important to test with the exact formulation of the culprit drug, as well as all the ingredients including excipients.

Concepts: Pharmacology, Asthma, Drug, Mast cell, Illness, Pharmaceutical drug, Excipients, Polyethylene glycol

2

Adjuvant treatment with interferon-alpha-2a (IFN) improved disease free survival (DFS) and showed a trend for improving overall survival (OS) in melanoma. This trial was designed to examine whether PEG-IFN is superior to IFN with regard to distant metastasis free survival (DMFS), DFS and OS.

Concepts: Improve, Interferon, Melanoma, Hepatitis B, Adjuvant, Polyethylene glycol

1

Sustained and controllable release of insulin is strongly required to achieve the ideal treatment of diabetes. We previously developed “self-assembly PEGylation retaining activity (SPRA) technology” via a host-guest interaction between PEGylated β-cyclodextrin and adamantane-appended insulin, and resulting PEGylated insulin was termed SPRA-insulin. So far, we also demonstrated that covalently PEGylated insulin forms polypseudorotaxanes (PPRXs) with cyclodextrins (PPRX technology). In the present study, we designed and evaluated the combination system of SPRA technology and PPRX technology to achieve a sustained and controllable release system of insulin. SPRA-insulin formed PPRXs with α-cyclodextrin and γ-cyclodextrin. In addition, SPRA-insulin/cyclodextrin PPRXs provided sustained and controllable release of insulin beyond the each single technology both in vitro and in vivo. These results suggest that the combination system of SPRA technology and PPRX technology is useful for design of a sustained and controllable release system of insulin.

Concepts: Present, Diabetes mellitus, In vivo, In vitro fertilisation, In vitro, Polyethylene glycol, PEGylation

1

Treatments for functional constipation (FC) and irritable bowel syndrome with constipation (IBS-C) differ, but symptom criteria do not reliably distinguish between them; some regard FC and IBS-C as parts of a single constipation spectrum. Our goal was to review studies comparing FC and IBS-C to identify possible biomarkers that separate them. A systematic review identified 15 studies that compared physiologic tests in FC vs IBS-C. Pain thresholds were lower in IBS-C than FC for 3/5 studies and not different in 2/5. Colonic motility was decreased more in FC than IBS-C for 3/3 studies, and whole gut transit was delayed more in FC than IBS-C in 3/8 studies and not different in 5/8. Pelvic floor dyssynergia was unrelated to diagnosis. Sympathetic arousal, measured in only one study, was greater in IBS-C than FC. The most reliable separation of FC from IBS-C was shown by a novel new magnetic resonance imaging technique described in this issue of the journal. These authors showed that drinking one liter of polyethylene glycol laxative significantly increased water content in the small intestine, volume of contents in the ascending colon, and time to first evacuation in FC vs IBS-C; and resulted in less colon motility and delayed whole gut transit in FC compared to IBS-C. Although replication is needed, this well-tolerated, non-invasive test promises to become a new standard for differential diagnosis of FC vs IBS-C. These data suggest that FC and IBS-C are different disorders rather than points on a constipation spectrum.

Concepts: Magnetic resonance imaging, Constipation, Gastroenterology, Irritable bowel syndrome, Flatulence, Dietary fiber, Polyethylene glycol, Laxative

1

This study aimed to reduce the common discomfort of colonoscopy patients when taking a bowel cleansing solution. Gum chewing, a form of sham feeding, was examined as a possible efficient intervention to reduce the discomfort from consuming polyethylene glycol.

Concepts: Ulcerative colitis, Abdominal pain, Colonoscopy, Gastroenterology, Bowel obstruction, Gastroenteritis, Polyethylene glycol, Whole bowel irrigation

0

Magnesium lithospermate B (MLB) is an active polyphenol acid with multiple pharmacological activities and poor oral bioavailability. The present research aimed to construct MLB loaded solid lipid nanoparticles (MLB-SLNs) for oral delivery to enhance its bioavailability. MLB-SLNs were prepared by solvent diffusion method and subsequently modified with polyethylene glycol monostearate (PEG-SA) superficially. The particle sizes of MLB-SLNs varied from 82.57 to 53.50nm with an improved drug loading capacity (up to 16.18%) after PEG-SA modification. Pharmacokinetic study indicated that Cmax (peak plasma MLB concentration) and AUC (area under curve) of MLB-SLNs increased significantly compared to that of MLB solution in male SD rats. The relative bioavailability of MLB-SLNs with PEG-SA modification was 753.98% compared to MLB solution administered by tail intravenous injection. The enhanced transport mechanism could be further illustrated by the results that MLB-SLNs showed higher permeability across Madin-Daby canine kidney (MDCK) epithelial cell monolayer and MLB-SLNs with smaller particle size distribution and PEG-SA modification manifested stronger cellular internalization ability on MDCK cells. Thus, PEG-SA modified solid lipid nanoparticles confirmed with enhanced cellular transport and improved oral bioavailability can be a promising oral MLB delivery system.

Concepts: Pharmacology, Petroleum, Epithelium, Particle size distribution, Pharmacokinetics, Biopharmaceutics Classification System, Bioavailability, Polyethylene glycol

0

Complications of the intrathecal route may cause potential toxicity related to the medical device and properties of the administered drug and/or excipient. A description of clinical and histological effects of polyethylene glycol and miripirium after Depo-Medrol injection, and the adverse reactions of particulate methylprednisolone acetate was conducted. The safety of the intrathecal route with excipients, label and off-label drugs is discussed.

Concepts: Pharmacology, Adverse drug reaction, Route of administration, Intrathecal, Polyethylene glycol, Excipient, Methylprednisolone