Defining the COX inhibitor selectivity of NSAIDs: Implications for understanding toxicity

Expert Review of Clinical Pharmacology

Volumn 3, Issue 6, 2010, Pages 769-776

  Knights, Kathleen M ^a   Mangoni, Arduino A ^b   Miners, John O ^a  

^a FLINDERS UNIVERSITY   (Australia)

^b UNIVERSITY OF ABERDEEN   (United Kingdom)

Author keywords

COX selectivity; COX 1; COX 2; human whole blood assay; IC50 values; in vitro models; NSAIDs; time dependent inhibition

Indexed keywords

ACETYLSALICYLIC ACID; CELECOXIB; CYCLOOXYGENASE 1; DICLOFENAC; FLURBIPROFEN; IBUPROFEN; INDOMETACIN; KETOPROFEN; MECLOFENAMIC ACID; MEFENAMIC ACID; NAPROXEN; NIMESULIDE; NONSTEROID ANTIINFLAMMATORY AGENT; PIROXICAM; PROSTACYCLIN; PROSTAGLANDIN SYNTHASE INHIBITOR; RECOMBINANT PROTEIN; THROMBOXANE A2;

CARDIOTOXICITY; CARDIOVASCULAR RISK; DRUG INHIBITION; DRUG MECHANISM; DRUG SELECTIVITY; ENZYME STRUCTURE; EXPERIMENTAL MODEL; GASTROINTESTINAL TOXICITY; HUMAN; IC 50; IN VITRO STUDY; NEPHROTOXICITY; NONHUMAN; REVIEW; THROMBOCYTE;

EID: 78649357770     PISSN: 17512433     EISSN: None     Source Type: Journal    
DOI: 10.1586/ecp.10.120     Document Type: Review

References (47)

1. Vane JR. Inhibition of prostaglandin synthesis as a mechanism of action of aspirin-like drugs. Nat. New Biol. 231, 232-235 (1971).
2. Cohen MM, Pollet JM. Prostaglandin E prevents aspirin and indomethacin damage to human gastric mucosa. Surg. Forum 27, 400-401 (1976).
3. Simmons DL, Botting RM, Hla T. COX isozymes: the biology of prostaglandin synthesis and inhibition. Pharmacol. Rev. 56, 387-437 (2004).
4. Marnett LJ. COX mechanisms. Curr. Opin. Chem. Biol. 4, 545-552 (2000).
5. Botting RM. COX: past, present and future. A tribute to John R Vane (1927-2004). J. Ther. Biol. 31, 208-219 (2006).
6. Picot D, Loll PJ, Graviton RM. The X-ray crystal structure of the membrane protein prostaglandin H synthase-1. Nature 367(2)243-249 (1994).
7. Kurumbail RG, Stevens AM, Gierse JK et al. Structural basis for selective inhibition of COX-2 by anti-infammatory agents. Nature 384, 644-648 (1996).
8. Rowlinson SW, Crews BC, Lanzo CA, Marnett LJ. The binding of arachidonic acid in the COX active site of mouse prostaglandin endoperoxide synthase-2 (COX-2): a putative L-shaped binding conformation utilizing the top channel region. J. Biol. Chem. 274, 23305-23310 (1999).
9. Rieke CJ, Mulichak AM, Garavito RM, Smith WL. The role of arginine 120 of human prostaglandin endoperoxide H synthase-2 in the interaction with fatty acid substrates and inhibitors. J. Biol. Chem. 274, 17109-17114 (1999).
10. Warner TD, Mitchell JA. COXs: new forms, new inhibitors, and lessons from the clinic. FASEB J. 18, 790-804 (2004).
11. Kozak KR, Crews BC, Morrow JD et al. Metabolism of the endocannabinoids, 2-arachidonylglycerol and anandamide, into prostaglandin, thromboxane, and prostacyclin glycerol esters and etanolamides. J. Biol. Chem. 277, 44877-44885 (2002).
12. Bozza PT, Magalhaes KG, Weller PF. Leukocyte lipid bodies-biogenesis and functions in infammation. Biochim. Biophys. Acta 1791, 540-551 (2009).
13. White JG. Platelet structure. In: Platelets (2nd Edition). Michelson AD (Ed.). Academic Press, London, UK, 45-73 (2007).
14. Ebbeling L, Robertson C, McNicol A, Gerrard JM. Rapid ultrastructural changes in the dense tubular system following platelet activation. Blood 80, 718-723 (1992).
15. Gerrard JM, White JG, Rao GHR, Townsend D. Localization of platelet prostaglandin production in the platelet dense tubular system. Am. J. Pathol. 83, 283-294 (1976).
16. Weber AA, Przytulski B, Schumacher M et al. Flow cytometry ana lysis of platelet COX-2 expression: induction of platelet COX-2 in patients undergoing coronary artery bypass grafting. Br. J. Haematol. 117, 424-426 (2002).
17. Lagarde M, Guichardant M, Menashi S, Crawford N. The phospholipids and fatty acid composition of human platelet surface and intracellular membranes isolated by high voltage free fow electrophoresis. J. Biol. Chem. 257, 3100-3104 (1982).
18. Cipollone F, Rocca B, Patrono C. COX-2 expression and inhibition in atherothrombosis. Arterioscler. Thromb. Vasc. Biol. 24, 246-255 (2004).
19. Grosser T, Fries S, Fitzgerald GA. Biological basis for the cardiovascular consequences of COX-2 inhibition: therapeutic challenges and opportunities. J. Clin. Invest 116, 4-15 (2006).
20. Flavahan NA. Balancing prostanoid activity in the human vascular system. Trends Pharmacol. Sci. 28, 106-110 (2007).
21. Pairet M, van Ryn J. Experimental models used to investigate the differential inhibition of COX-1 and COX-2 by non-steroidal anti-infammatory drugs. Infamm. Res. 47(Suppl. 2), S93-S101 (1998).
22. Polasek TM, Miners JO. In vitro approaches to investigate mechanism-based inactivation of CYP enzymes. Expert Opin. Drug Metab. Toxicol. 3, 321-329 (2007).
23. Swinney DC, Mak AY, Barnett J, Ramesha CS. Differential allosteric regulation of prostaglandin H synthase 1 and 2 by arachidonic acid. J. Biol. Chem. 272, 12393-12398 (1997).
24. Chen W, Pawelek TR, Kulmacz RJ. Hydroperoxide dependence and cooperative COX kinetics in prostaglandin H synthase-1 and-2. J. Biol. Chem. 274, 20301-20306 (1999).
25. Battistini B, Botting R, Bakhle YS. COX-1 and COX-2: toward the development of more selective NSAIDs. Drug News Perspect. 7, 501-512 (1994).
26. Walker MC, Kurumbail RG, Kiefer JR et al. A three-step kinetic mechanism for selective inhibition of cyclo-oxygenase-2 by diarylheterocyclic inhibitors. Biochem. J. 357, 709-718 (2001).
27. Dannhardt G, Kiefer W COX inhibitors-current status and future prospects. Eur. J. Med. Chem. 36, 109-126 (2001).
28. Smith WL, De Witt DL, Garavito RM. COXs: structural, cellular and molecular biology. Annu. Rev. Biochem. 69, 145-182 (2000).
29. 2 and time independent inhibitors elicit identical enzyme conformations. Biochemistry 40, 5172-5180 (2001).
30. Patrignani P, Panara MR Greco A et al. Biochemical and pharmacological characterization of the COX activity of human blood prostaglandin endoperoxide synthases. J. Pharmacol. Exp. Ther. 271, 1705-1712 (1994).
31. Brooks P, Emery P, Evans JF et al Interpreting the clinical signifcance of the differential inhibition of cyclooxygenase-1 and cyclooxygenase-2. Rheumatology 38, 779-788 (1999).
32. Warner TD, Giuliano F, Vojnovic I, Bukasa A, Mitchell JA. Nonsteroid drug selectivities for cyclo-oxygenase-1 rather than cyclo-oxygenase-2 are associated with human gastrointestinal toxicity: a full in vitro ana lysis. Proc. Natl Acad. Sci. USA 96, 7563-7568 (1999).
33. Laufer S, Greim C, Luik S, Ayoub SS, Dehner F. Human whole blood assay for rapid and routine testing of non-steroidal anti-infammatory drugs (NSAIDs) on cyclo-oxygenase-2 activity Infammopharmacology 16, 155-161 (2008).
34. Riendeau D, Percival MD, Brideau C et al Etoricoxib (MK-0663): preclinical profle and comparison with other agents that selectively inhibit COX-2. J. Pharmacol. Exp. Ther. 296, 558-566 (2001).
35. De Leval X, Delarge J, Devel P et al Evaluation of classical NSAIDs and COX-2 selective inhibitors on purifed ovine enzymes and human whole blood. Prostaglandins Leukot. Essent. Fatty Acids 64, 211-216 (2001).
36. Blain H, Boileau C, Lapicque F et al. Limitations of the in vitro whole blood assay for predicting the COX selectivity of NSAIDs in clinical use. Br. J. Clin. Pharmacol. 53, 255-265 (2002).
37. Warner TD, Vojnovic I, Bishop-Bailey D, Mitchell JA. Infuence of plasma protein on the potencies of inhibitors of cyclooxygenase-1 and-2. FASEB J. 20(3), 542-544 (2006).
38. Miners JO, Mackenzie PI, Knights KM. The prediction of drug-glucuronidation parameters in humans; UDP-glucuronosyltransferase enzyme-selective substrate and inhibitor probes for reaction phenotyping and in vitro-in vivo extrapolation of drug clearance and drug-drug interaction potential. Drug Metab. Rev. 42, 196-208 (2010).
39. Brown CM, Reisfeld B, Mayeno AN. Cytochromes P450: a structural-based summary of biotransformations using representative substrates. Drug Metab. Rev. 40, 1-100 (2008).
40. Laneuville O, Breuer DK, Dewitt DL, Hla T, Funk CD, Smith WL. Differential inhibition of human prostaglandin endoperoxide H synthases-1 and-2 by nonsteroidal anti-infammatory drugs. J. Pharmacol. Exp. Ther. 271, 927-934 (1994).
41. Salinas G, Rangasetty UC, Uretsky BF, Birnbaum Y The cycloxygenase 2 (COX-2) story: it's time to explain, not infame. J. Cardiovasc. Pharmacol. Ther. 12, 98-111 (2007).
42. Warner TD, Mitchell JA. COX-2 selectivity alone does not defne the cardiovascular risks associated with non-steroidal anti-infammatory drugs. Lancet 371, 270-273 (2008).
43. Aneja A, Farkouh ME. Adverse cardiovascular effects of NSAIDs: driven by blood pressure, or edema? Ther. Advan. Cardiovasc. Dis. 2, 53-66 (2008).
44. White WB. Cardiovascular effects of the COX inhibitors. Hypertension 49, 408-418 (2007).
45. Vane JR, Botting RM. New insights into the mode of action of anti-infammatory drugs. Infamm. Res. 44, 1-10 (1995).
46. Gierse JK, Hauser SD, Creely DP et al. Expression and selective inhibition of the constitutive and inducible forms of human cyclo-oxygenase. Biochem. J. 305, 479-484 (1995).
47. Cromlish WA, Kennedy BP. Selective inhibition of COX-1 and-2 using intact insect cell assays. Biochem. Pharmacol. 52, 1777-1785 (1996).