INFLUENCE OF MELOXICAM ON FUROSEMIDE PHARMACOKINETICS AND PHARMACODYNAMICS IN HEALTHY-VOLUNTEERS

Fifteen healthy male volunteers participated in an open, multiple-dose study to investigate a possible interaction between furosemide and meloxicam, a new non-steroidal anti-inflammatory agent (NSAID). The study comprised three treatment periods. First, furosemide (40 mg) was administered as a single oral daily dose for 3 days. A wash-out day was followed by the administration of meloxicam (15 mg) as a single oral daily dose for 10 days. Thereafter, meloxicam and furosemide were administered concomitantly at the same doses as described above, for 3 days. The effect of concomitant ingestion of meloxicam and furosemide on furosemide-induced diuresis, urine and serum electrolytes, and furosemide pharmacokinetics was determined, after both single and repeated administration of furosemide. Estimates of the ''(furosemide + meloxicam)/(furosemide alone)'' mean ratio of the variable AUC(0-infinity) for plasma furosemide and the cumulative sodium excretion (0-8 h) were 97.4% (90% confidence interval 89.7-106%) and 88% (90% confidence interval 82-94%), respectively. The study results indicate that meloxicam does not affect the pharmacokinetics of furosemide in healthy volunteers, nor does it affect furosemide-induced diuresis or serum electrolytes. The cumulative urinary electrolyte excretion after concomitant administration of meloxicam and furosemide is somewhat lower than after administration of furosemide alone, in particular for the period 0-8 h after administration of furosemide. This effect of meloxicam on furosemide dynamics is small, and is probably not clinically relevant in healthy volunteers under the dosing regime studied.