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.