Effects of celecoxib and naproxen on renal function in nonazotemic patients with cirrhosis and ascites.
Nonselective inhibition of cyclooxygenase (COX) by nonsteroidal anti-inflammatory drugs frequently induces renal failure in decompensated cirrhosis. Studies in experimental cirrhosis suggest that selective inhibitors of the inducible isoform COX-2 do not adversely affect renal function. However, very limited information is available on the effects of these compounds on renal function in human cirrhosis. This investigation consists of a double-blind, randomized, placebo-controlled trial aimed at comparing the effects of the selective COX-2 inhibitor celecoxib (200 mg every 12 hours for a total of 5 doses) on platelet and renal function and the renal response to furosemide (40 mg intravenously) with those of naproxen (500 mg every 12 hours for a total of 5 doses) and placebo in 28 patients with cirrhosis and ascites. A significant reduction (P < .05) in glomerular filtration rate (113 +/- 27 to 84 +/- 22 mL/min), renal plasma flow (592 +/- 158 to 429 +/- 106 mL/min) and urinary prostaglandin E(2) excretion (3430 +/- 430 to 2068 +/- 549 pg/min) and suppression of the diuretic (urine volume: 561 +/- 128 to 414 +/- 107 mL/h) and natriuretic (urine sodium: 53 +/- 13 to 34 +/- 10 mEq/h) responses to furosemide were observed in the group of patients treated with naproxen but not in the other two groups. Naproxen, but not celecoxib or placebo, significantly inhibited platelet aggregation (72% +/- 8% to 47% +/- 8%, P < .05) and thromboxane B(2) production (41 +/- 12 to 14 +/- 5 pg/mL, P < .05). In conclusion, our results indicate that short-term administration of celecoxib does not impair platelet and renal function and the response to diuretics in decompensated cirrhosis. Further studies are needed to evaluate the long-term safety of this drug in cirrhosis.
Clària
Joan
J
DNA Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
Kent
Jeffrey D
JD
López-Parra
Marta
M
Escolar
Ginés
G
Ruiz-Del-Arbol
Luís
L
Ginès
Pere
P
Jiménez
Wladimiro
W
Vucelic
Boris
B
Arroyo
Vicente
V
D001201:Ascites / Q000503:physiopathology*; D000068579:Celecoxib; D015232:Dinoprostone / Q000096:biosynthesis; D004311:Double-Blind Method; D005260:Female; D005665:Furosemide / Q000494:pharmacology; D005919:Glomerular Filtration Rate; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008103:Liver Cirrhosis / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009288:Naproxen / Q000009:adverse effects*; D010974:Platelet Aggregation / Q000187:drug effects; D011720:Pyrazoles / Q000009:adverse effects*; D012083:Renin / Q000097:blood; D013449:Sulfonamides / Q000009:adverse effects*
D011720:Pyrazoles; D013449:Sulfonamides; D009288:Naproxen; D005665:Furosemide; D012083:Renin; D000068579:Celecoxib; D015232:Dinoprostone