Tolevamer

Tolevamer (free acid)

Systematic (IUPAC) name
Poly(styrol-4-sulfonic acid)
Clinical data
Legal status	development terminated
Routes of administration	oral
Pharmacokinetic data
Bioavailability	not significantly absorbed from the gut
Metabolism	not metabolised
Excretion	N/A
Identifiers
CAS Registry Number	28210-41-5
ATC code	None
Chemical data
Formula	(C8H8O3S)n
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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-acquired 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.^[1]

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.^[1][2]

Dosage

Six grams of tolevamer potassium sodium were applied per day, but up to 15 g were tolerated well by most patients.^[2]

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.^[3]

References