Product Details

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 sevre diarrhea. Diacerein is under investigation for the treatment of Insulin Resistance, Diabetes Mellitus (Type 2), and Diabetes-Related Complications.

Indication

For the treatment of osteoarthritis affecting the hip or knee.

Pharmacodynamics

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

Mechanism of action

Diacerein's active metabolite rhein Rhein reduces cartilage destruction by decreasing expression of matrix metalloproteinase (MMP)-1 and -3 as well as upregulating tissue inhibitor of matrix metalloproteinases which serve to reduce the activity of several MMPs. The anti-inflammatory action of rhein reduces the level of interleukin-1beta activity which plays a large role in reduction of extracellular matrix production, MMP activity, and continued inflammation. Rhein reduces abnormal osteoblast synthetic activity through an unknown mechanism.

Absorption

Bioavailability of 50-60% [1]. Entirely converted to the active metabolite rhein Rhein before reaching systemic circulation.

Volume of distribution

15-60L [1].

Protein binding

99% of rhein is bound to plasma proteins [1].

Metabolism

Entirely converted to rhien Rhein through double deacetylation before reaching systemic circulation [1]. Rhein Rhein is further metabolized to rhein glucuronide and rhein sulfate.

• Diacerein
   
  Rhein

Route of elimination

37% excreted in urine and 53% in feces as estimated in rats [2].

Half life

4-10h [1].

Clearance

Total CL is 1.5L/h and renal CL is 0.1L/h [1].

Toxicity

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

source:drugbank