Tolevamer

Drugbox
drug_name = Tolevamer (free acid)
IUPAC_name = Poly(styrol-4-sulfonic acid)

---

width = 100
CAS_number =
CAS_supplemental =
ATC_prefix =
ATC_suffix =
ATC_supplemental =
PubChem =
DrugBank =
chemical_formula = (C₈H₈O₃S)_n
molecular_weight =
smiles =
bioavailability = Not significantly absorbed from the gut
protein_bound =
metabolism = Not metabolised
elimination_half-life =
excretion = N/A
pregnancy_AU =
pregnancy_US =
pregnancy_category=
legal_AU =
legal_CA =
legal_UK =
legal_US =
legal_status = Investigational
routes_of_administration = Oral

Tolevamer is a toxin binding polymer that was investigated by Genzyme for the treatment of "Clostridium difficile" associated diarrhoea (CDAD).

Background

"Clostridium difficile" is a major cause of hospital-aquired diarrhoea, affecting about 300,000 patients in the U.S. alone. CDAD typically occurs after treatment with antibiotics which disrupt the gut flora, allowing "C. difficile" to proliferate in the gut and release enterotoxins which lead to diarrhoea. CDAD is usually treated with the antibiotics vancomycin, metronidazole or both. This therapy yields good results but has the disadvantage of further disrupting the flora.cite journal
author = H. Spreitzer
date = September 24, 2007
title = Neue Wirkstoffe - Tolevamer
journal = Österreichische Apothekerzeitung
issue = 20/2007
pages = 955
language = German ]

Mechanism of action

Tolevamer was designed to bind the enterotoxins rather than attack "C. difficile" directly. Since it has no antibiotic properties, it does not harm the gut flora. Early studies used the sodium salt, but it was soon replaced with the potassium sodium salt to prevent hypokalaemia which is often associated with diarrhoea.cite journal
author = Wang, Y, Serradell, N, Rosa, E, Bolos, J
title = Tolevamer Potassium Sodium
journal = Drugs of the Future
year = 2007
volume = 32
issue = 6
pages = 501-505 ]

Dosage

6 g of tolevamer potassium sodium were applied per day, but up to 15 g were tolerated well by most patients.

Termination of development

In early 2008, a noninferiority study versus vancomycin or metronidazole found that about half of the patient in the tolevamer group did not complete the treatment, versus 25% in the vancomycin and 29% in the metronidazole groups.

CDAD recurrence in patients reaching clinical success was reduced significantly by tolevamer (6% recurrence rate), vancomycin (18%) and metronidazole (19%). However, the good result of tolevamer is partly due to the high drop-out rate in this group.

Since tolevamer did not reach its primary endpoint in this study, the development was halted. [ [http://www.medscape.com/viewarticle/573449 Medscape.com: Tolevamer Less Effective Than Standard Therapies for "C difficile"–Associated Diarrhea] ]

References