Study on the possible interaction between tenoxicam and furosemide

Abstract

A possible interaction between furosemide and the non-steroidal antiinflammatory drug (NSAID) tenoxicam was investigated in 12 patients (6 males, 6 females) with mild heart insufficiency and with a need for antiinflammatory treatment. The patients received once daily doses of 40 mg furosemide over 15 days. From day 6 onwards until day 13 tenoxicam was concurrently administered: 20 mg b.i.d. on days 6 and 7 and 20 mg once a day on days 8 through 13. On days 0 (pre-check), 1, 3, 5, 9, 12 and 15 vital parameters were measured and urine quantitatively collected to assess the elimination of a series of biochemical determinants. The urinary excretion profiles of furosemide and trough plasma levels of tenoxicam were measured on days 5, 9, 12 and 15. Vital parameters (blood pressure, heart rate, ECG and body weight) were not affected by tenoxicam. The urinary excretion of sodium and chloride tended to decrease during treatment with tenoxicam, but this effect was not significant. Tenoxicam caused a significant drop of prostaglandin E2 (PGE2) in 12-h urine of both gender: from 601 +/- 397 ng on day 5 to 264 +/- 117 ng on day 9 for men and from 128 +/- 78 ng on day 5 to 67 +/- 55 ng on day 9 for women. Creatinine clearance, beta 2-microglobulin clearance and urinary excretion of N-acetyl-glucosaminidase did not reveal evidence for acute renal impairment. The urinary excretion profile of furosemide was not significantly changed by concurrent dosing of tenoxicam. The drop in PGE2 excretion was likely a direct effect of tenoxicam on the synthesis of renal prostaglandins.