Disease relevance of Fisiodar

• Diacerhein in the treatment of osteoarthritis of the hip [1].
• OBJECTIVE: To evaluate the ability of diacerein, an interleukin-1beta inhibitor, to slow the progressive decrease in joint space width observed in patients with hip osteoarthritis (OA) [2].
• OBJECTIVE: To evaluate the efficacy and safety of diacerein, a drug with interleukin-1beta--inhibitory activity in vitro, in patients with knee osteoarthritis (OA) [3].
• Except for moderate and transient digestive disturbances (soft stools, diarrhoea), diacerein is well tolerated and seems neither responsible for gastrointestinal bleeding nor for renal, liver or haematological toxicity [4].
• In the adjuvant-induced arthritic rats, diacerein at 100 mg/kg/day significantly suppressed the paw edema and the increase in serum mucoprotein [5].

Psychiatry related information on Fisiodar

• In the same range of doses, diacerhein or gabapentin did not affect the locomotor activity, motor coordination, or body temperature of the animals [6].
• Medical and paramedical procedures carried out in addition to those stipulated in the protocol (medical consultations, physiotherapy, nursing, etc.), osteoarthritis-related, were fewer and less costly in the diacerein plus standard therapy group than in the standard therapy group [7].

High impact information on Fisiodar

• Evaluation of the structure-modifying effects of diacerein in hip osteoarthritis: ECHODIAH, a three-year, placebo-controlled trial. Evaluation of the Chondromodulating Effect of Diacerein in OA of the Hip [2].
• METHODS: In this randomized, double-blind, placebo-controlled 3-year study, 507 patients with primary OA of the hip (by the American College of Rheumatology criteria) received diacerein (50 mg twice a day) or placebo [2].
• Efficacy and safety of diacerein in osteoarthritis of the knee: a double-blind, placebo-controlled trial. The Diacerein Study Group [3].
• Diacerein was significantly superior to placebo during the active treatment phase (Glass score, 1.50 [95% confidence interval, 0.80-2.20]) [8].
• Clinical pharmacokinetics of diacerein [4].

Chemical compound and disease context of Fisiodar

• To determine the efficacy and safety of diacerhein, a potential new therapeutic agent with properties differing from those of existing nonsteroidal anti-inflammatory drugs (NSAIDs), and of a combination of diacerhein and an NSAID (tenoxicam) in the treatment of osteoarthritis (OA) of the hip [1].
• Evaluation of the symptomatic and structural efficacy of a new hyaluronic acid compound, NRD101, in comparison with diacerein and placebo in a 1 year randomised controlled study in symptomatic knee osteoarthritis [9].
• OBJECTIVE: To evaluate the in vitro effects of diacerhein, a new drug for the treatment of osteoarthritis (OA), and its active metabolite, rhein, on the production of nitric oxide (NO), prostaglandin (PGE2), cyclooxygenase-2 (COX-2), as well as the production and expression of the inducible nitric oxide synthase (iNOS) in human OA chondrocytes [10].
• Rhein (R: 1,8-dihydroxy-3-carboxyanthraquinone) is the active metabolite of the drug diacerhein (DAR), an anthraquinone molecule which has recently been proposed for the long-term treatment of osteoarthrosis [11].
• Glucosamine, diacerein, and hyaluronan may all be disease-modifying drugs for osteoarthritis but confirmatory studies are still needed [12].

Biological context of Fisiodar

• Rhein kinetics after single oral doses of diacerein are linear in the range 50 to 200 mg [4].
• Short and practical total syntheses of rhein (1) and diacerhein (2) have been achieved via a Fries rearrangement and bis-carbonylation strategy followed by cyclization in molten salt, starting from dibromoester 7 [13].
• Diacerein reduces the excess synthesis of bone remodeling factors by human osteoblast cells from osteoarthritic subchondral bone [14].
• CONCLUSION: These results provide a novel regulatory mechanism by which diacerhein and rhein could exert a down-regulation on IL-1's effect on OA cartilage [15].
• CONCLUSION: We have demonstrated that rhein, an active metabolite of diacerein down-regulates the gene-expression and production of proMMPs and up-regulates the TIMP-1 production [16].

Anatomical context of Fisiodar

• Articular cartilage damage is reduced by diacerein in animal models of osteoarthritis [17].
• Diacerein largely prevents the metabolic alterations caused by cytokine exposure in human chondrocytes, possibly through its ability to block early intracellular mediators after cytokine stimulation, such as oxygen radicals [18].
• CONCLUSION: Diacerhein and rhein can effectively inhibit the synthesis of IL-1beta on human OA synovium, as well as the action of this cytokine at the cartilage level, by reducing the number of chondrocyte IL-1R [19].
• We studied the effects of diacerein and rhein on the metabolic and inflammatory variables of OA subchondral osteoblasts [14].
• RESULTS: The mean volume of synovial fluid obtained from the OA knee of the diacerhein-treated dogs was approximately 40% less than that from the OA knee of the controls [20].

Associations of Fisiodar with other chemical compounds

• METHODS: Levels of IL-1beta and TNF-alpha were determined using specific ELISA in culture medium of human synovial membrane explants incubated in the presence of 1 microg/ml of lipopolysaccharide with or without therapeutic concentrations of diacerhein (1.4, 2.7, 5.4 x 10(-5) M) and rhein (1.7, 3.5, 7.0 x 10(-5) M) [19].
• The treatment with diacerhein or with gabapentin also inhibited the mechanical allodynia induced by complete Freund's adjuvant (CFA) or after the partial ligation of the sciatic nerve (PLSN) [6].
• METHODS: Human OA chondrocytes were incubated in the presence or absence of 25 units/ml recombinant human interleukin-1beta (rhIL-1beta) with or without therapeutic concentrations of diacerhein and rhein at 5, 10, and 20 microg/ml and naproxen at 30 and 90 microg/ml [10].
• In the ovariectomized rats, diacerein (10, 100 mg/kg/day) also significantly prevented bone loss and reduced the serum alkaline phosphatase and decreased the excretion of urinary hydroxyproline [5].
• Diacerein is an anthraquinone molecule that has been shown to reduce the severity of OA, both in man and in animal models [21].

Gene context of Fisiodar

• Neither diacerhein nor rhein significantly affected the level of synthesis of TNF-alpha or the level of TNF-R [19].
• Inhibition of interleukin-1beta-induced activation of MEK/ERK pathway and DNA binding of NF-kappaB and AP-1: Potential mechanism for Diacerein effects in osteoarthritis [22].
• Diacerhein and rhein reduce the interleukin 1beta stimulated inducible nitric oxide synthesis level and activity while stimulating cyclooxygenase-2 synthesis in human osteoarthritic chondrocytes [10].
• In contrast, IGF-1 levels only increased slightly when cells were treated with rhein but not with diacerein [14].
• Of the metabolic factors, they inhibited the production of uPA, with rhein showing slightly more potency; inhibitions of 69% and 57% were reached at the highest concentration (20 microg/ml) of rhein and diacerein, respectively [14].

Analytical, diagnostic and therapeutic context of Fisiodar

• RESULTS: In the intent-to-treat population, 100 mg/day diacerein (50 mg twice daily) was significantly superior (P < 0.05) to placebo using the primary criterion (visual analog scale [VAS] assessment of pain on movement) [3].
• RESULTS: Diacerhein treatment slowed the progression of OA, as measured by grading of gross changes in the unstable knee at arthroscopy 16 weeks after cruciate ligament transection (P = 0.04) and at the time the animals were killed, 32 weeks after surgery (P = 0.05) [23].
• METHODS: Electronic databases were searched for randomized controlled trials with diacerein [8].
• A meta-analysis of controlled clinical studies with diacerein in the treatment of osteoarthritis [8].
• In clinical trials of < or = 6 months' duration, oral diacerein 50mg twice daily was associated with improvement in 57 to 85% of patients with osteoarthritis [17].

References