Pharmacokinetics of dexketoprofen trometamol in subjects with mild and moderate chronic renal insufficiency.
The influence of mild to moderate chronic renal insufficiency on the pharmacokinetics of dexketoprofen trometamol was evaluated. Dexketoprofen was administered to volunteers with mild (n = 8) or moderate (n = 8) renal impairment and to healthy subjects (n = 8), as a single 12.5 mg oral dose (equivalent to 18.5 mg of the tromethamine salt). All subjects completed the study and no serious adverse events were recorded. Mild and moderate renal insufficiency increased Cmax by approximately 22% and 37%, respectively, as related to normal subjects (p < 0.05 for moderate renal dysfunction). No statistically significant differences between groups were obtained for tmax, AUC, CL/F, renal CL and V/F. The cumulative urinary excretion of unchanged dexketoprofen, assessed up to 24 hours postdose, was similar in all groups (median values of 7.0%, 8.1% and 9.7% of the administered dose). On the contrary, cumulative urinary excretions of conjugated dexketoprofen decreased in subjects with mild or moderate renal insufficiency when compared to healthy controls (median and 95% CI for differences: -3.3% (-14.8% to 2.6%) and -7.3% (-22.2% to -0.2%), respectively). Conservatively, a dose adjustment of dexketoprofen in patients with impaired renal function is recommended.
Valles
J
J
Menarini Research, Clinical Department, Badalona, Spain.
Artigas
R
R
Mas
M
M
Crea
A
A
Muller
F
F
Paredes
I
I
Capriati
A
A
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007660:Ketoprofen / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000378:metabolism*; D012720:Severity of Illness Index; D014325:Tromethamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
D000894:Anti-Inflammatory Agents, Non-Steroidal; D014325:Tromethamine; D007660:Ketoprofen; C118296:dexketoprofen trometamol