Influence of renal function on the pharmacokinetics of diacerein after a single oral dose.
The pharmacokinetics of diacerein (a new anti-inflammatory analgesic antipyretic drug) following a single oral dose of 50 mg was studied in 12 healthy volunteers and two groups of eight patients with mild or severe renal insufficiency. Statistical analysis using a Kruskal-Wallis rank sum test showed a significant difference between the three groups for the following parameters. In severely uraemic patients, median AUC0-infinity was multiplied by a factor of ca 2: 40.5 mg h/l versus 21.3 in healthy subjects, P = 0.04; and t1/2 was prolonged by the same factor: 9.6 h versus 4.3 in the control group, P = 0.003. Apparent drug availability and renal clearance assessed through urinary data decreased with renal failure, respectively: 14.5% and 0.045 l/h versus 35.4% (P = 0.01) and 0.13 l/h (P = 0.008) in healthy subjects. Amounts of glucuro and sulfo conjugates in urine were lower in severely uraemic patients. Intermediate values were observed for mildly uraemic patients. Other parameters: lag-time, Cmax, tmax, Vss/F, urinary glucuro- to sulphoconjugate ratios did not change significantly. Apparent total clearance of rhein was poorly correlated with creatinine clearance and this was related to a decrease of non-renal clearance of rhein in renal insufficiency. It was concluded that, from a pharmacokinetic point of view, a reduction (50%) in the maintenance dosage of diacerein should be considered in severe renal failure.
Debord
P
P
Department of Pharmacotoxicology, Avicenne Hospital, Bobigny, France.
Louchahi
K
K
Tod
M
M
Molinier
P
P
Berdah
L
L
Perret
G
G
Petitjean
O
O
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000880:Anthraquinones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003404:Creatinine / Q000097:blood / Q000652:urine; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D051437:Renal Insufficiency / Q000097:blood / Q000378:metabolism*
D000880:Anthraquinones; D000894:Anti-Inflammatory Agents, Non-Steroidal; C025292:diacerein; D003404:Creatinine; C020491:rhein