Ketoprofen pharmacokinetics in the elderly: influence of rheumatic disease, renal function, and dose

An age-related accumulation of ketoprofen due to a reduced clearance has been reported in the elderly. Other studies have not observed these changes in the kinetics of unchanged ketoprofen, but have reported increased plasma levels and reduced urinary excretion of conjugated ketoprofen. The authors examined the effects of dose, renal function, and the presence of arthritis on the stereoselective kinetics of ketoprofen in five nonarthritic and six arthritic elderly subjects. There was a significant difference in renal function (CLCr, mL/min; arthritic, 71.8 +/- 12.3, nonarthritic, 91.4 +/- 11.1), but not in age or weight between the two groups. Subjects received 50 mg and then 150 mg enteric-coated racemic ketoprofen, and plasma and urine samples were collected for 24 hours. No significant differences in CL/F, area under the curve (AUC), half-life (t1/2), time to reach peak concentration (tmax), or maximum peak plasma concentration (Cmax) were found between groups or between doses, and values were similar to those previously reported in young adults. Urinary ketoprofen conjugate (S:R) ratio was 1.6 +/- .25 and 1.65 +/- .27 for arthritic and nonarthritic subjects. Greater amounts of conjugated ketoprofen enantiomers were present in the plasma of the arthritic compared with nonarthritic subjects. Renal clearance of ketoprofen conjugates exhibited stereoselectivity (R > S), and was decreased in the arthritic group. Significant changes in the kinetics of unchanged ketoprofen was not found to occur in elderly subjects in the presence or absence of rheumatic disease or moderate renal impairment.(ABSTRACT TRUNCATED AT 250 WORDS)