Non-Systemic Drugs: A Critical Review

@article{Charmot2012NonSystemicDA,
  title={Non-Systemic Drugs: A Critical Review},
  author={Dominique Campbell Charmot},
  journal={Current Pharmaceutical Design},
  year={2012},
  volume={18},
  pages={1434 - 1445}
}
  • D. Charmot
  • Published 31 March 2012
  • Medicine, Biology
  • Current Pharmaceutical Design
Non-systemic drugs act within the intestinal lumen without reaching the systemic circulation. The first generation included polymeric resins that sequester phosphate ions, potassium ions, or bile acids for the treatment of electrolyte imbalances or hypercholesteremia. The field has evolved towards non-absorbable small molecules or peptides targeting luminal enzymes or transporters for the treatment of mineral metabolism disorders, diabetes, gastrointestinal (GI) disorders, and enteric… 
View PDF
62 Citations
Highly Influential Citations
1
Background Citations
26

62 Citations

Citation Type

Citation Type

Non-systemic Intestine-Targeted Drugs.
  • M. Fyfe
  • Biology, Medicine
    Progress in medicinal chemistry
  • 2016
Intestinal targeting of drugs: rational design approaches and challenges.
TLDR
Examples of various approaches to intestinal targeting are provided, challenges and areas in need of future scientific advances are discussed, and the potential for new treatments to be developed are discussed.
Fluoroquinolones: novel class of gastrointestinal dietary lipid digestion and absorption inhibitors
TLDR
Three new fluoroquinolones (11, 12, and 13) were synthesized and evaluated in vitro with respect to their anti-lipase efficacy and potency properties and gave IC50 values in the range of 18.4–29.1 μM against PL, which could be used to advance the development of anti-obesity drugs via the regulation of the entire gastrointestinal lipolysis process.
Polymeric bile acid sequestrants: Review of design, in vitro binding activities, and hypocholesterolemic effects.
Exploratory studies with NX-13: oral toxicity and pharmacokinetics in rodents of an orally active, gut-restricted first-in-class therapeutic for IBD that targets NLRX1
TLDR
NX-13 is safe and well-tolerated in rats given oral doses as high as 1000 mg/kg with a favorable gastrointestinal localized pharmacokinetic profile, confirming NX-13 as a promising therapeutic for Crohn’s disease and ulcerative colitis.
Design of Gut-Restricted Thiazolidine Agonists of G Protein-Coupled Bile Acid Receptor 1 (GPBAR1, TGR5).
TLDR
A series of gut-restricted TGR5 agonists that elicit a potent response in mice, with minimal gallbladder-related effects are described, a compound with minimal systemic availability that may have therapeutic value to patients with type 2 diabetes mellitus, nonalcoholic steatohepatitis, or inflammatory bowel disease.
Polymers as drugs—Advances in therapeutic applications of polymer binding agents
TLDR
The properties of polymer drugs, particularly sequestrants, are reviewed, with an emphasis on recent advances in polymer properties which may enhance the utility of this class of drugs.
Non-absorbable mesoporous silica for the development of protein sequestration therapies.
The importance of intake: a gut feeling.
TLDR
Even if the tenapanor-induced reduction in sodium adsorption is limited in humins, combination ofTenapanor therapy with diuretics may be an interesting option in selected patients.
New therapeutic perspectives in irritable bowel syndrome: Targeting low-grade inflammation, immuno-neuroendocrine axis, motility, secretion and beyond
TLDR
This literature review aims to summarize the findings related to new and investigational therapeutic agents for IBS, most recently developed in preclinical as well as Phase 1 and Phase 2 clinical studies.
...
...

References

SHOWING 1-10 OF 175 REFERENCES
Membrane transporters in drug development
TLDR
Overall, it is advised that the timing of transporter investigations should be driven by efficacy, safety and clinical trial enrolment questions, as well as a need for further understanding of the absorption, distribution, metabolism and excretion properties of the drug molecule, and information required for drug labelling.
Lipid-lowering drugs acting at the level of the gastrointestinal tract.
TLDR
This review considers the hypolipidaemic drugs that act on the gastrointestinal (GI) tract and Orlistat-assisted weight loss improves the overall lipid profile, carbohydrate metabolism and transaminase activities, but its use should be limited to weight reduction.
Bile acid reabsorption inhibitors (BARI): novel hypolipidemic drugs.
TLDR
Specific inhibitors of the ileal bile acid transporter belonging to different chemotypes have been developed in recent years for this purpose, some now entering clinical stage and an overview on the molecular target, the discovery of specific inhibitors and respective optimization strategies is presented.
New uremic toxins - which solutes should be removed?
TLDR
New therapeutic strategies pursuing specific removal of protein-bound solutes and/or pharmacological neutralization of the molecular impact of the responsible compounds are explored, aiming at an improved outcome in CKD patients.
Biologically active polymeric sequestrants: Design, synthesis, and therapeutic applications
TLDR
This report highlights recent developments in the rational design and synthesis of appropriate functional polymers that have resulted in a number of promising polymer-based therapeutic agents, including some marketed products.
Intestinal permeability and its relevance for absorption and elimination
  • H. Lennernäs
  • Biology
    Xenobiotica; the fate of foreign compounds in biological systems
  • 2007
TLDR
The determined jejunal Peff for drugs transported mainly by absorptive carriers will accurately predict the fraction of the dose absorbed as a consequence of the regional expression, and the data show that the human intestinal epithelium has a large resistance towards large and hydrophilic compounds.
Current strategies used to enhance the paracellular transport of therapeutic polypeptides across the intestinal epithelium.
Inhibition of apical sodium-dependent bile acid transporter as a novel treatment for diabetes.
TLDR
It is demonstrated that inhibition of Asbt increases bile acids in the distal intestine, promotes Glp-1 release and may offer a new therapeutic strategy for type 2 diabetes mellitus.
Linaclotide is a potent and selective guanylate cyclase C agonist that elicits pharmacological effects locally in the gastrointestinal tract.
Soft drug design: General principles and recent applications
TLDR
An overview of the general soft drug design principles is presented and a variety of specific examples to illustrate the concepts are provided to systematize and summarize the related work done in a number of laboratories.
...
...