Hartmann D, Kleinbloesem C H, Lücker P W, Vetter G
Pharma Clinical Research Department, F. Hoffmann-La Roche & Co. Ltd., Basle, Switzerland.
Arzneimittelforschung. 1987 Sep;37(9):1072-6.
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.
在12例(6例男性,6例女性)轻度心力衰竭且需要抗炎治疗的患者中,研究了速尿与非甾体抗炎药(NSAID)替诺昔康之间可能存在的相互作用。患者在15天内每日接受40mg速尿的剂量。从第6天起至第13天同时给予替诺昔康:第6天和第7天每日两次,每次20mg,第8天至第13天每日一次,每次20mg。在第0天(预检查)、第1天、第3天、第5天、第9天、第12天和第15天测量生命体征参数,并定量收集尿液以评估一系列生化指标的排泄情况。在第5天、第9天、第12天和第15天测量速尿的尿排泄曲线和替诺昔康的谷血浆水平。生命体征参数(血压、心率、心电图和体重)不受替诺昔康影响。在使用替诺昔康治疗期间,钠和氯的尿排泄量有下降趋势,但这种影响不显著。替诺昔康导致两性12小时尿液中前列腺素E2(PGE2)显著下降:男性从第5天的601±397ng降至第9天的264±117ng,女性从第5天的128±78ng降至第9天的67±55ng。肌酐清除率、β2-微球蛋白清除率和N-乙酰葡糖胺酶的尿排泄量未显示急性肾功能损害的证据。同时给予替诺昔康后,速尿的尿排泄曲线没有显著变化。PGE2排泄量的下降可能是替诺昔康对肾前列腺素合成的直接作用。