Publisher: Rafa Laboratories Ltd, POB 405, Jerusalem 91003
ANTI-ARTHROSIQUE
(M: MUSCLE AND SKELETON)
Diacerein is an anthraquinone derivative which has moderate anti-inflammatory activity. It is anti-inflammatory at high doses and devoid of any irritant effect on the stomach.
Action onset is slow, beginning towards day 30 of treatment and becoming significant after about 45 days. It has an additive effect in combination with NSAIDs.
In vitro, diacerein has the following properties:
In some models, diacerein stimulates production of proteoglycans, glycosaminoglycans and hyaluronic acid.
A positive effect on cartilage has been demonstrated in a number of animal models.
A multicentre, randomized, double-blind, placebo-controlled, three year study (ECHODIAH study) assessing the eefect of diacerein on the radiological Joint Space (JSW) has been conducted on 507 patients with an osteoarthritis of the hip. Patients received either 50 mg of deacerein (n=255) or placebo (n=252) twice a day, i.e. in the morning and in the evening.
Main efficacy criteria were:
269 patients copleted the trial.
At 3 years, the Intend-To-Treat (ITT) analysis shows that:
Orally administered diacerein undergoes a hepatic first-pass effect and is totally deacetylated to the sulphoconjugated metabolite, rhein. After a single 50 mg dose, plasma diacerein concentrations peak arises at a mean 2.5 hours and the maximal concentration is of the order of 3 mg/l. ART 50 mg capsule intake with food increases the bioavailability (the area under the curve increases by nearly 25%) and delays absorption.
The pharmacokinetic parameters of single doses of ART 50 mg, capsule ranging from 50 to 200 mg are dose-independent.
Protein binding is very strong (99%) and mainly consists in high-affinity binding to albumin.
The elimination half-life of rhein is approximately 4.5 hours. The total quantity excreted in the urine is around 30%. 80% of the rhein excreted in urine is in sulpho- and glucuroconjugated form and 20% is excreted in unchanged form.
Repeated administration of ART 50 mg, capsule (50 mg twice daily) results in slight accumulation. In patients with severe kidney failure (creatinine clearance less than 30 ml/min), the area under the curve and elimination half-life are doubled and urinary elimination halved.
Given the good clinical safety profile of the drug, doses do not need to be adjusted in elderly patients despite the slower elimination.
Not applicable.
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