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Influence of renal function on the pharmacokinetics of diacerein after a single oral dose
Author(s) -
Debord P.,
Louchahi K.,
Tod M.,
Molinier P.,
Berdah L.,
Perret G.,
Petitjean O.
Publication year - 1993
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.1993.tb01039.x
Subject(s) - pharmacokinetics , medicine , renal function , urinary system , antipyretic , urine , creatinine , analgesic , urology , gastroenterology , pharmacology
Summary— 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 AUC 0‐∞ was multiplied by a factor of ca 2: 40.5 mg h/l versus 21.3 in healthy subjects, P = 0.04; and t 1/2 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, C max , t max , V ss /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.