Are Some NSAIDs Safer Than Others?
Sulindac has an unusual metabolic pathway and has been proposed to be less nephrotoxic than other NSAIDs. Indeed, sulindac gets converted into its active sulfide metabolite in the liver, which does not appear in the urine. Sulindac sulfide itself gets inactivated to the sulfoxide metabolite which also does not have an effect on prostaglandin production in the kidney. However, the studies which showed the beneficial effect of this drug likely had an insufficient duration of usage to appreciate the full pharmacologic effect. A study which described the effect of this drug in comparison with indomethacin in patients with chronic stable renal function showed no effect on creatinine clearance or body weight with sulindac. But the latter was associated with decreased urinary prostaglandin E2 (PGE2) and sodium excretion, although of lesser magnitude compared with indomethacin. A subsequent study comparing these two in patient with normal renal function showed a similar magnitude of decreased urinary sodium and PGE2 excretion. As discussed before, fenoprofen, phenacetin and possibly indomethacin may have a greater propensity to cause harm. Though it seemed that ibuprofen resulted a statistically higher renal event rate than celecoxib or naproxen in a recent trial, the different doses used (2400 mg for ibuprofen versus 200 mg for celecoxib) may have had a role to play in that.
Curr Opin Nephrol Hypertens. 2019;28(2):163-170. © 2019 Lippincott Williams & Wilkins