Clinical Pharmacokinetics of Diacerein

Abstract

Diacerein is a drug for the treatment of patients with osteoarthritis. This drug is administered orally as 50 mg twice daily. Diacerein is entirely converted into rhein before reaching the systemic circulation. Rhein itself is either eliminated by the renal route (20%) or conjugated in the liver to rhein glucuronide (60%) and rhein sulfate (20%); these metabolites are mainly eliminated by the kidney. The pharmacokinetics characteristics of diacerein are about the same in young healthy volunteers and elderly people with normal renal function, both after a single dose (50 mg) or repeated doses (25 to 75 mg twice daily). Rhein kinetics after single oral doses of diacerein are linear in the range 50 to 200 mg. However, rhein kinetics are time-dependent, since the nonrenal clearance decreases with repeated doses. This results in a moderate increase in maximum plasma concentration, area under the plasma concentration-time curve and elimination half-life. Nevertheless, the steady-state is reached by the third administration and the mean elimination half-life is then around 7 to 8 hours. Taking diacerein with a standard meal delays systemic absorption, but is associated with a 25% increase in the amount absorbed. Mild-to-severe (Child Pugh's grade B to C) liver cirrhosis does not change the kinetics of diacerein, whereas mild-to-severe renal insufficiency (creatinine clearance < 2.4 L/h) is followed by accumulation of rhein which justifies a 50% reduction of the standard daily dosage. Rhein is highly bound to plasma proteins (about 99%), but this binding is not saturable so that no drug interactions are likely to occur, in contrast to those widely reported with nonsteroidal anti-inflammatory drugs. 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.

Chitosan-coated diacerein nanosuspensions as a platform for enhancing bioavailability and lowering side effects: preparation, characterization, and ex vivo/in vivo evaluation

“…47 It was noticed that all permeated drug was measured as rhein, which agreed with previous reports that DCN is completely converted into rhein before reaching the circulation. 48 As shown in Figure 5, the cumulative amounts permeated after 120 minutes were 450.48±10.51, 108.28±1.06, and 97.83±6.53 µg for DNS-F7, CS-DNS-F10, and DCN suspension, respectively. Although there are too many reports suggesting that CS has a permeation enhancement effect 21 either θ Figure 4 Powder X-ray powder diffraction (A) and scanning electron microscopy (B) of DNs-F7 and cs-DNs-F10.…”

Comparative Analysis of Efficacy and Safety of Diacerein Versus S-Adenosyl Methionine in the Management of Osteoarthritis of Knee Joint

“…Patients treated with SAMe had complaints of mild gastritis. The major AE reported with diacerein was discoloration of urine, due to the elimination of its metabolites via the kidney, which is of no clinical significance [24]. Although the incidence of diarrhoea was higher in the diacerein group, the event may be considered more as patient discomfort.…”

Clinical Study on the Effects of Diacerein and Diacerein Combined with Chondroitin Sulfate on Canine Hip Osteoarthritis

“…In a cartilage explant model, it was found that diacerein and rhein could reduce the levels of caspase-3 and iNOS [12] . Previous studies have reported that diacerein is safer than non-steroidal anti-inflammatory drugs [1,13,14] . Moreover, it can even be used in cases of renal and liver impairment [14] .…”