Investigation of plasma levels of etodolac and urine PGE2 in patients with rheumatoid arthritis

: 13 women patients (containing high-aged, mean age 71.9 years) with rheumatoid arthritis (RA) (10 with normal renal function and 3 with moderate renal insufficiency) participated in a 5-day study to assess the effects of etodolac on renal function and the necessity of dose adjustment. After no drug-free day, etodolac, 200 mg b.i.d. was started. The plasma levels of etodolac were similar in both normal control in phase I studies and throughout this study. Although the mean urine PGE2 concentration in renal insufficient group was significantly lower than that of normal renal function group, the mean urine PGE2 concentration in after etodolac administration was not different from that in before its administration in each group. This result suggested that renal adverse reactions with etodolac were low in incident. Moreover, it was required to consider that glucocorticoid might influence renal and/or hepatic excretion of etodolac. In this study the glucocorticoid was tend to be administrated in the patients with moderate renal insufficiency. Those glucocorticoid group showed lower levels of etodolac in blood serum (monitored by AUC0-8, day 4 Cmin and day 5 Cmin) than non-glucocorticoid group did, but not significantly. Interestingly, there is a negative correlation (r = -0.442) between AUC0-8 at day 1 and urine PGE2 at day 5 in glucocorticoid group. The levels of etodolac in blood serum in normal renal function group were also not significant in difference from that in the moderate renal insufficient group. These results suggest that the dose adjustment of etodolac in high-aged RA patients with moderate renal insufficiency can be excluded.