Effects of celecoxib and diclofenac on blood pressure, renal function, and vasoactive prostanoids in young and elderly subjects.
Cyclooxygenase (COX) inhibitors are among the most widely used drugs, especially in the elderly. It has been claimed that the new COX-2 inhibitors offer advantages in terms of drug safety. To test this hypothesis, the authors compared in a double-blind, randomized trial the effects of celecoxib (200 mg bid) and diclofenac (75 mg bid) on blood pressure and renal function in two groups (each n = 12) of young (mean age = 32 years) and elderly (mean age = 68 years) normotensive subjects. Changes from baseline in the 24-hour blood pressure profiles, parameters of the renin-angiotensin-aldosterone system, inulin clearance, urinary marker proteins, and eicosanoid excretion were monitored during the treatment period of 2 weeks. Comparison between celecoxib and diclofenac showed no significant difference in minor alterations of blood pressure. During daytime, there was a trend to elevation of mean arterial blood pressure (mmHg) by celecoxib in the elderly of 2.8 (95 % confidence interval [CI) = -2.5 to 8.2) in comparison with the young subjects of -1.3 (95% CI= -3.7 to 1.0); there was also a trend to elevation of mean arterial blood pressure by diclofenac in the elderly of 4.1 (95% CI= -1.2 to 9.4) in comparison with the young subjects of 0.4 (95% CI= -2.4 to 3.2). In both populations, the authors found no significant drug effects on the parameters of the renin-angiotensin-aldosterone system, inulin clearance, and urinary marker proteins. As expected, diclofenac reduced excretion of allprostanoids, whereas celecoxib did not affect production of TxB2 and its metabolites. Neither in young nor in elderly normotensive subjects were blood pressure and renal function significantly affected by a short-term treatment with standard doses of celecoxib and diclofenac. Therefore, normal aging appears not to represent a special risk factor in therapy with these two agents.
Dilger
Karin
K
Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.
Herrlinger
Charlotte
C
Peters
Jörg
J
Seyberth
Hannsjörg W
HW
Schweer
Horst
H
Klotz
Ulrich
U
D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D015415:Biomarkers; D001794:Blood Pressure / Q000187:drug effects*; D000068579:Celecoxib; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004008:Diclofenac / Q000494:pharmacology*; D004311:Double-Blind Method; D015777:Eicosanoids / Q000652:urine; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007444:Inulin; D007527:Isoenzymes / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects*; D007677:Kidney Function Tests; D008297:Male; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism*; D011507:Proteinuria / Q000378:metabolism; D011720:Pyrazoles; D012084:Renin-Angiotensin System / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology*; D013997:Time Factors
D015415:Biomarkers; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D015777:Eicosanoids; D007527:Isoenzymes; D008565:Membrane Proteins; D011453:Prostaglandins; D011720:Pyrazoles; D013449:Sulfonamides; D004008:Diclofenac; D007444:Inulin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib