title: An evaluation of the interaction of meloxicam with frusemide in patients with compensated chronic cardiac failure.
abstract: OBJECTIVE
  To evaluate the interaction of meloxicam with frusemide in patients with compensated cardiac failure.
  
  
  METHODS
  Nineteen patients with Grade II or III compensated chronic cardiac failure completed this randomized, double-blind, cross-over study. The patients received 40 mg frusemide day(-1) for 7 days. Thereafter, patients received either 15 mg meloxicam plus 40 mg frusemide day(-1), or one placebo tablet plus 40 mg frusemide day(-1) for 7 days. After a washout period of 7 days during which patients received 40 mg frusemide day(-1) for 7 days, the patients were crossed over to the alternate treatment. The effect of concomitant ingestion of meloxicam and frusemide on frusemide-induced diuresis, urine and serum electrolytes, urinary frusemide excretion, and plasma frusemide pharmacokinetics was also determined.
  
  
  RESULTS
  The estimate (90% confidence interval) of the '(frusemide + meloxicam)/(frusemide alone)' mean ratio of the variables Cmax, AUC(SS) and Cmax/AUC(SS) for plasma frusemide were 121% (101% to 145%), 106% (96.4% to 117%), and 114% (98.3% to 132%), respectively. Similarly, the estimate (90% confidence interval) of the '(frusemide + meloxicam)/(frusemide alone)' of the mean ratio of the variable cumulative urinary frusemide excretion after multiple doses of frusemide were 123% (101% to 150%) for the period 0-8 h, and 122% (105% to 142%) for the period 0-24 h after drug administration on day 7. The estimate (90% confidence interval) of the '(frusemide + meloxicam)/(frusemide alone)' mean ratio of the pharmacodynamic variables cumulative sodium excretion was 105% (95.2% to 116%) for the period 0-8 h and 108% (96.5% to 121%) for the period 0-24 h after drug administration on day 7.
  
  
  CONCLUSIONS
  Meloxicam may lead to slightly increased maximum concentrations of frusemide in plasma, as well as to slightly increased urinary excretion of frusemide, without affecting the pharmacodynamics of frusemide. Thus there is no clinically significant pharmacokinetic or pharmacodynamic interaction of meloxicam with frusemide following repeated co-administration of meloxicam and frusemide to patients with compensated chronic cardiac failure.
authors.affiliation: FARMOVS Research Centre for Clinical Pharmacology and Drug Development, Department of Pharmacology, University of the Orange Free State, Bloemfontein, South Africa.
authors.forename: F O
authors.initials: FO
authors.lastname: Müller
authors.forename: M V
authors.initials: MV
authors.lastname: Middle
authors.forename: R
authors.initials: R
authors.lastname: Schall
authors.forename: J
authors.initials: J
authors.lastname: Terblanché
authors.forename: H K
authors.initials: HK
authors.lastname: Hundt
authors.forename: G
authors.initials: G
authors.lastname: Groenewoud
mesh_terms: D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D019540:Area Under Curve; D018592:Cross-Over Studies; D004232:Diuretics / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004311:Double-Blind Method; D004347:Drug Interactions; D004573:Electrolytes / Q000097:blood; D005260:Female; D005665:Furosemide / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006207:Half-Life; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D008297:Male; D000077239:Meloxicam; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D013843:Thiazines / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004232:Diuretics; D004573:Electrolytes; D013843:Thiazines; D013844:Thiazoles; D005665:Furosemide; D000077239:Meloxicam