Pharmacology of cyclooxygenase-2 inhibition in the kidney.
Cyclooxygenase (COX) exists as two unique isoforms (that is, COX-1 and COX-2) which are poorly understood with regard to their roles in renal function. The renal effects of conventional non-steroidal anti-inflammatory drugs (NSAIDs) are believed to result from the inhibition of one or both isoforms. Drugs that selectively inhibit COX-2 provide useful pharmacological tools for discerning the effects associated with the inhibition of the individual isoforms, and may help clarify the renal roles of COX-1 and COX-2. This review summarizes the current data on the renal expression of COX isoforms and their potential roles in renal function, and reviews the studies that have attempted to correlate renal functional changes with selective isoform inhibition. Since there are significant differences in the expression of COX isoforms in the kidneys of laboratory animals and humans, this review also examines the correlation of the results of COX inhibition in experimental studies in laboratory animals with clinical data. Because of potential interspecies differences in the roles of COX isoforms in renal function, animal models may have limited predictive value for patients, particularly those with renal risk factors. Accordingly, any uncertainty concerning the safety or therapeutic benefit of COX-2-specific drugs in these patient populations will need to be resolved with clinical investigations.
Khan
Kanwar Nasir M
KN
Pharmacia Research & Development, Skokie, Illinois 60077, USA. nasir.k.khan@pharmacia.com
Paulson
Susan K
SK
Verburg
Kenneth M
KM
Lefkowith
James B
JB
Maziasz
Timothy J
TJ
D000818:Animals; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D005314:Embryonic and Fetal Development / Q000502:physiology; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism* / Q000502:physiology; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology*; D008565:Membrane Proteins; D009318:Natriuresis / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism* / Q000502:physiology; D012079:Renal Circulation / Q000187:drug effects
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases