Tolevamer is a toxin

Toxin

A toxin is a poisonous substance produced within living cells or organisms; man-made substances created by artificial processes are thus excluded...

 binding polymer

Polymer

A polymer is a large molecule composed of repeating structural units. These subunits are typically connected by covalent chemical bonds...

 that was investigated by Genzyme

Genzyme

Genzyme Corporation is a fully owned subsidiary of Sanofi-Aventis. Before its acquisition, Genzyme was an American biotechnology company based in Cambridge, Massachusetts. In 2010, Genzyme was the world’s third-largest biotechnology company, employing more than 11,000 people around the world...

 for the treatment of Clostridium difficile

Clostridium difficile

Clostridium difficile , also known as "CDF/cdf", or "C...

associated diarrhoea (CDAD).

Background

Clostridium difficile is a major cause of hospital-acquired diarrhoea, affecting about 300,000 patients in the U.S. alone. CDAD typically occurs after treatment with antibiotic

Antibiotic

An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...

s which disrupt the gut flora

Gut flora

Gut flora consists of microorganisms that live in the digestive tracts of animals and is the largest reservoir of human flora. In this context, gut is synonymous with intestinal, and flora with microbiota and microflora....

, allowing C. difficile to proliferate in the gut and release enterotoxin

Enterotoxin

An enterotoxin is a protein toxin released by a microorganism in the intestine. Enterotoxins are chromosomally encoded exotoxins that are produced and secreted from several bacterial organisms. They are often heat-stable, and are of low molecular weight and water-soluble...

s which lead to diarrhoea. CDAD is usually treated with the antibiotics vancomycin

Vancomycin

Vancomycin INN is a glycopeptide antibiotic used in the prophylaxis and treatment of infections caused by Gram-positive bacteria. It has traditionally been reserved as a drug of "last resort", used only after treatment with other antibiotics had failed, although the emergence of...

, metronidazole

Metronidazole

Metronidazole is a nitroimidazole antibiotic medication used particularly for anaerobic bacteria and protozoa. Metronidazole is an antibiotic, amebicide, and antiprotozoal....

 or both. This therapy yields good results but has the disadvantage of further disrupting the flora.

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

Sodium

Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...

 salt, but it was soon replaced with the potassium

Potassium

Potassium is the chemical element with the symbol K and atomic number 19. Elemental potassium is a soft silvery-white alkali metal that oxidizes rapidly in air and is very reactive with water, generating sufficient heat to ignite the hydrogen emitted in the reaction.Potassium and sodium are...

 sodium salt to prevent hypokalaemia which is often associated with diarrhoea.

Dosage

Six grams 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.