Pharmacokinetics and Cardiovascular Effect of Etoricoxib in the Absence or Presence of St. John’s Wort in Rats

Abstract

Objectives:

The effect of chronic administration of etoricoxib (EXB), in the absence or presence of St. John’s Wort (SJW), on its pharmacokinetic parameters and blood pressure was investigated in rats.

Methods:

Rats were divided into 3 groups, each group received daily different oral treatment for 3 weeks. Rats’ blood pressures were monitored initially, after 1 and 3 weeks of treatment, and after 1 week of discontinuing dosing of both drugs. EXB pharmacokinetic parameters in the absence or presence of SJW were calculated after 3 weeks.

Key findings:

SJW was significantly affected EXB pharmacokinetic parameters. The steady state peak plasma concentration and terminal half-life were reduced by 32% and 91%, respectively, due to a > 3 fold increase in its apparent clearance which is a concentration and time dependent effect. EXB was significantly increased (P<0.001) Rats’ blood pressure while, co-administration of EXB and SJW was not significantly affect (P>0.05) rats’ blood pressure as compared to the control.

Conclusions:

Monitoring blood pressure of patients anticipated taking EXB for extended period should be advised. The co-administration of SJW with EXB should be avoided since SJW would greatly reduce EXB concentrations by inducing its metabolism.

Key words

etoricoxib - St. John’s Wort - pharmacokinetics - blood pressure - rats

• References

• 1 Katz N. Coxibs: Evolving role in pain management. Seminars in Arthritis and Rheumatism 2002; 32 3 (Suppl. 01) 15-24
• 2 Matsumoto AK, Cavanaugh PF Jr. Etoricoxib. Drugs of Today 2004; 40: 395-414
• 3 Hawley C. COX-2 inhibitors. Lancet 1999; 353: 307
• 4 Simmons DL, Botting RM, Hla T. Cyclooxygenase isozymes: the biology of prostaglandin synthesis and inhibition. Pharmacol Rev 2004; 56: 387-437
• 5 Prasit P, Wang Z, Brideau C et al. The discovery of rofecoxib, [MK 966, Vioxx, 4-(4′-methylsulfonylphenyl) 3-phenyl-2(5H)-furanone], an orally active cyclooxygenase -2-inhibitor. Bioorg Med Chem Lett 1999; 9: 1773-1778
• 6 Chan CC, Boyce S, Brideau C et al. Rofecoxib [Vioxx, MK-0966; 4-(4′-methylsulfonylphenyl)-3-phenyl-2-(5H)-furanone]: a potent and orally active cyclooxygenase-2 inhibitor. Pharmacological and biochemical profiles. Pharmacol Exp Ther 1999; 290: 551-560
• 7 Penning TD, Talley JJ, Bertenshaw SR et al. Synthesis and biological evaluation of the 1,5-diarylpyrazole class of cyclooxygenase-2 inhibitors: identification of 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] benze nesulfonamide (SC-58635, celecoxib). J Med Chem 1997; 40: 1347-1365
• 8 Chauret N, Yergey JA, Brideau C et al. In Vitro Metabolism Considerations, Including Activity Testing of Metabolites, in the Discovery and Selection of the COX-2 Inhibitor Etoricoxib (MK-0663). Bioorg Med Chem Lett 2001; 11: 1059-1062
• 9 Bombardier C, Laine L, Reicin A et al. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. N Engl J Med 2000; 343: 1520-1528
• 10 Bertagnolli MM, Eagle CJ, Zauber AG et al. Celecoxib for the prevention of sporadic colorectal adenomas. N Engl J Med 2006; 355: 873-884
• 11 Ott E, Nussmeier NA, Duke PC et al. Efficacy and safety of the cyclooxygenase 2 inhibitors parecoxib and valdecoxib in patients undergoing coronary artery bypass surgery. J Thorac Cardiovasc Surg 2003; 125: 1481-1492
• 12 Solomon SD, McMurray JJ, Pfeffer MA et al. Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med 2005; 352: 1071-1080
• 13 Nussmeier NA, Whelton AA, Brown MT et al. Complications of the COX-2 inhibitors parecoxib and valdecoxib after cardiac surgery. N Engl J Med 2005; 352: 1081-1091
• 14 Bresalier RS, Sandler RS, Quan H et al. Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med 2005; 352: 1092-1102
• 15 Kearney PM, Baigent C, Godwin J et al. Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials. BMJ 2006; 332: 1302-1308
• 16 Catella-Lawson F, McAdam B, Morrison BW et al. Effects of specific inhibition of cyclooxygenase-2 on sodium balance, hemodynamics, and vasoactive eicosanoids. J Pharmacol Exp The 1999; 289: 735-741
• 17 McAdam BF, Catella-Lawson F, Mardini IA et al. Systemic biosynthesis of prostacyclin by cyclooxygenase (COX)-2: The human pharmacology of a selective inhibitor of COX-2. Proc Natl Acad Sc U.S.A 1999; 96: 272-277
• 18 Brater DC, Anderson SA, Brown-Cartwright D et al. Effects of nonsteroidal anti-inflammatory drugs on renal function: Focus of cyclooxygenase-2- selective inhibition. Am J Med 1999; 107: 565-570
• 19 Riendeau D, Percival MD, Brideau C et al. Etoricoxib (MK-0663): preclinical profile and comparison with other agents that selectively inhibit cyclooxygenase-2. J Pharm Exp Ther 2001; 296: 558-566
• 20 Dallob A, Hawkey CJ, Greenberg H et al. Characterization of etoricoxib, a novel, selective COX-2 inhibitor. J Clin Pharmacol 2003; 43: 573-585
• 21 Takemoto JK, Reynolds JK, Remsberg CM et al. Clinical pharmacokinetic and pharmacodynamic profile of etoricoxib. Clin Pharmacokinet 2008; 47: 703-720
• 22 Cochrane DJ, Jarvis B, Keating GM. Etoricoxib. Drugs 2002; 62: 2637-2651
• 23 Agrawal NG, Porras AG, Matthews CZ et al. Dose proportionality of oral etoricoxib, a highly selective cyclooxygenase-2 inhibitor, in healthy volunteers. J Clin Pharmacol 2001; 41: 1106-1110
• 24 Schwartz JI, Thach C, Lasseter KC et al. Effects of Etoricoxib and Comparator Nonsteroidal Anti-Inflammatory Drugs on Urinary Sodium Excretion, Blood Pressure, and Other Renal Function Indicators in Elderly Subjects Consuming a Controlled Sodium Diet. J Clin Pharmacol 2007; 47: 1521-1531
• 25 Cannon CP, Curtis SP, FitzGerald GA et al. Cardiovascular outcomes with etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) programme: a randomised comparison. Lancet 2006; 368: 1771-1781
• 26 Wheaton AG, Blanck HM, Gizlice Z et al. Medicinal herb use in a population-based survey of adults: prevalence and frequency of use, reasons for use, and use among their children. Ann Epidemiol 2005; 15: 678-685
• 27 McNaughton SA, Mishra GD, Paul AA et al. Supplement use is associated with health status and health related behaviors in the 1946 British birth cohort. J Nutr 2005; 135: 1782-1789
• 28 Peng CC, Glassman PA, Trilli LE et al. Incidence and severity of potential drug–dietary supplement interactions in primary care patients: an exploratory study of 2 outpatient practices. Arch Intern Med 2004; 164: 630-636
• 29 Bailey DG, Dresser GK. Natural products and adverse drug interactions. CMAJ 2004; 170: 1531-1532
• 30 Morrow JD, Edeki TI, El Mouelhi M et al. American Society for Clinical Pharmacology and Therapeutics position statement on dietary supplement safety and regulation. Clin Pharmacol Ther 2005; 77: 113-122
• 31 Linde K, Ramirez G, Mulrow CD et al. John’s Wort for depression – an overview and meta-analysis of randomized clinical trials. BMJ 1996; 313: 253-258
• 32 Gaster B, Holroyd J. St John’s Wort for depression. Arch Intern Med 2000; 160: 152-156
• 33 Morris CA, Avorn J. Internet Marketing Herbal Products. JAMA 2003; 290: 1505-1509
• 34 Fugh-Berman A, Ernst E. Herb–drug interactions: review and assessment of report reliability. Br J Clin Pharmacol 2001; 52: 587-595
• 35 Dresser GK, Schwarz UI, Wilkinson GR et al. Coordinate induction of both cytochrome P4503A and MDR1 by St John’s wort in healthy subjects. Clin Pharmacol Ther 2003; 73: 41-50
• 36 Markowitz JS, Donovan JL, DeVane CL et al. Effect of St John’s Wort on drug metabolism by induction of cytochrome P450 3A4 enzyme. JAMA 2003; 290: 1500-1504
• 37 Kawaguchi A, Ohmori M, Tsuruoka S et al. Drug interaction between St John’s wort and quazepam. Br J Clin Pharmacol 2004; 58: 403-410
• 38 Nebel A, Schneider BJ, Baker RK et al. Potential metabolic interaction between St. John’s wort and theophylline. Ann Pharmacother 1999; 33: 502
• 39 Murakami Y, Tanaka T, Murakami H et al. Pharmacokinetic modelling of the interaction between St John’s wort and ciclosporin A. Br J Clin Pharmacol 2006; 61: 671-676
• 40 Radwan MA, Zaghloul IY, Abd Elbaky NA. Stability indicating high performance liquid chromatographic assay for the pharmacokinetics of Cyclooxygenase (COX-2) inhibitor etoricoxib in rats. Afr J Pharm Pharmacol 2009; 3: 339-346
• 41 Gibaldi M, Perrier D. Pharmacokinetics. 2^nd Ed. New York: Marcel Dekker Inc.; 1982
• 42 Solomon DH, Schneeweiss S, Levin R et al. The relationship between COX-2 specific inhibitors and hypertension. Hypertension 2004; 44: 140-145
• 43 Dürr D, Stieger B, Kullak-Ublick GA et al. John’s Wort induces intestinal Pglycoprotein/MDR1 and intestinal and hepatic CYP3A4. Clin Pharmacol Ther 2000; 68: 598-604
• 44 Ruschitzka F, Meier PJ, Turina M et al. Acute heart transplant rejection due to Saint John’s wort. Lancet 2000; 355: 548-549
• 45 Piscitelli SC, Burstein AH, Chaitt D et al. Indinavir concentrations and St John’s wort. Lancet 2000; 355: 547-548
• 46 Johne A, Brockmöller J, Bauer S et al. Pharmacokinetic interaction of digoxin with an herbal extract from St John’s wort (Hypericum perforatum). Clin Pharmacol Ther 1999; 66: 338-345
• 47 Frye RF, Fitzgerald SM, Lagattuta TF et al. Effect of St John’s wort on imatinib mesylate pharmacokinetics. Clin Pharmacol Ther 2004; 76: 323-329
• 48 Schwarz UI, Büschel B, Kirch W. Unwanted pregnancy on selfmedication with St John’s wort despite hormonal contraception. Br J Clin Pharmacol 2003; 55: 112-113
• 49 Mai I, Störmer E, Bauer S et al. Impact of St John’s wort treatment on the pharmacokinetics of tacrolimus and mycophenolic acid in renal transplant patients. Nephrol Dial Transplant 2003; 18: 819-822
• 50 Bennett WM, Henrich WL, Stoff JS. The renal effects of nonsteroidal anti-inflammatory drugs: Summary and recommendations. Am J Kidney Dis 1996; 28 (Suppl. 01) 556-562
• 51 Whelton A, Hamilton CW. Nonsteroidal anti-inflammatory drugs: Effects on kidney function. J Clin Pharmacol 1991; 31: 588-598
• 52 Heerdink ER, Leufkens HG, Herings RM et al. NSAIDs associated with increased risk of congestive heart failure in elderly patients taking diuretics. Arch Intern Med 1998; 158: 1108-1112
• 53 De Leeuw PW. Nonsteroidal anti-inflammatory drugs and hypertension. The risks in perspective. Drugs 1996; 51: 179-187