Diacerein

Absorption

Bioavailability of 50-60% . Entirely converted to the active metabolite rhein Rhein before reaching systemic circulation.

Toxicity

Rhein Rhein has an oral LD50 of >5000mg/kg in mice. This is equivalent to a diacerein dose of >6476mg/kg.

Description

Diacerein is a disease-modifying antirheumatic drug (DMARD), reported to be useful in the treatment of various inflammatory conditions, including osteoarthritis. It forms water soluble chelates with calcium and copper, acting ultimately to reduce the activity of lysosomal enzymes and decrease the formation of rheumatoid factor.

The Uses of Diacerein

Diacerein is a diacetyl precursor of rhein, an anthraquinone found in plants. Rhein, at 10 μM, inhibits IL-1β signaling, suppressing signaling through NF-κB and AP-1, and reduces the expression of the matrix metalloproteases MMP-1 and MMP-13. Diacerein, presumably after conversion to rhein, down-regulates the expression of the IL-1β receptor on articular chondrocytes, enhances the expression of TGF-β, and increases collagen and aggrecan. It does not alter COX activity. It is mildly effective in ameliorating osteoarthritis.

Indications

For the treatment of osteoarthritis affecting the hip or knee .

Background

Diacerein is a prodrug which is metabolized to rhein. It is currently approved in France for the treatment of osteoarthritis although the use of diacerein is restricted due to the side effects including severe diarrhea . Diacerein is under investigation for the treatment of Insulin Resistance, Diabetes Mellitus (Type 2), and Diabetes-Related Complications.

What are the applications of Application

Diacerein is a tricyclic psuedo-phenanthrene showing interleukin-1 inhibition

Pharmacokinetics

Decreases inflammation and cartilage destruction and also corrects altered osteoblast acitivity .

Metabolism

Entirely converted to rhien Rhein through double deacetylation before reaching systemic circulation . Rhein Rhein is further metabolized to rhein glucuronide and rhein sulfate.