Pharmacokinetic and pharmacodynamic aspects of the ideal COX-2 inhibitor: a rheumatologist's perspective.
The ideal cyclooxygenase-2-specific inhibitor (coxib) would demonstrate efficacy comparable or superior to the best non-steroidal anti-inflammatory drug (NSAID) and, in addition to being substantially less gastrotoxic than the safest conventional NSAID, would have limited or no cardiovascular or renal toxicity and be generally tolerated as well as placebo. The contribution of the pharmacokinetic properties of a coxib to achieving this goal has been overlooked to some degree for available coxibs. Maximizing synovial compartment exposure while minimizing systemic exposure may deliver tolerability benefits, particularly with respect to rates of hypertension and cardiovascular and thrombotic adverse effects.
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Department of Clinical Pharmacology, St. Vincent's Hospital, Victoria Street, Darlinghurst, Sydney NSW 2010, Australia. r.day@unsw.edu.au
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000473:pathology; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006207:Half-Life; D006801:Humans; D007052:Ibuprofen / Q000493:pharmacokinetics; D007527:Isoenzymes / Q000378:metabolism*; D008565:Membrane Proteins; D009288:Naproxen / Q000493:pharmacokinetics / Q000627:therapeutic use; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D012219:Rheumatology; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D009288:Naproxen; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D007052:Ibuprofen