Abstract
Purpose
The effect of topical miconazole oral gel and systemic oral voriconazole on the pharmacokinetics of oral etoricoxib was studied in 12 healthy volunteers.
Methods
Plasma concentrations of etoricoxib, miconazole, voriconazole, and thromboxane B2 generation were followed after ingestion of 60 mg etoricoxib without pretreatment, after topical administration of miconazole oral gel (85 mg × 3, 3 days), or after oral voriconazole (400 mg × 2, 1st day, 200 mg × 2, 2nd day).
Results
Etoricoxib area under the plasma concentration-time curve \(\left( {{\text{AUC}}_{0 - \infty } } \right)\) and maximum plasma concentration (Cmax) geometric mean ratios (GMR) with/without miconazole were 1.69 {90% confidence interval (CI); 1.46–1.92} and 1.12 (90% CI; 0.99–1.25), respectively, and corresponding GMRs with/without voriconazole were 1.49 (90% CI; 1.37–1.61) and 1.19 (90% CI; 1.08–1.31), respectively.
Conclusions
Miconazole oral gel and oral voriconazole produced comparable increase in the exposure to etoricoxib, presumably via CYP3A inhibition.
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References
Agrawal NG, Porras AG, Matthews CZ, Rose MJ, Woolf EJ, Musser BJ, Dynder AL, Mazina KE, Lasseter KC, Hunt TL, Schwartz JI, McCrea JB, Gottesdiener KM (2003) Single- and multiple-dose pharmacokinetics of etoricoxib, a selective inhibitor of cyclooxygenase-2, in man. J Clin Pharmacol 43:268–276
Rodrigues AD, Halpin RA, Geer LA, Cui D, Woolf EJ, Matthews CZ, Gottesdiener KM, Larson PJ, Lasseter KC, Agrawal NG (2003) Absorption, metabolism, and excretion of etoricoxib, a potent and selective cyclooxygenase-2 inhibitor, in healthy male volunteers. Drug Metab Dispos 31:224–232
Kassahun K, McIntosh IS, Shou M, Walsh DJ, Rodeheffer C, Slaughter DE, Geer LA, Halpin RA, Agrawal N, Rodrigues AD (2001) Role of human liver cytochrome P4503A in the metabolism of etoricoxib, a novel cyclooxygenase-2 selective inhibitor. Drug Metab Dispos 29:813–820
Niwa T, Shiraga T, Takagi A (2005) Effect of antifungal drugs on cytochrome P450 (CYP) 2C9, CYP2C19, and CYP3A4 activities in human liver microsomes. Biol Pharm Bull 28:1805–1808
Niwa T, Inoue-Yamamoto S, Shiraga T, Takagi A (2005) Effect of antifungal drugs on cytochrome P450 (CYP) 1A2, CYP2D6, and CYP2E1 activities in human liver microsomes. Biol Pharm Bull 28:1813–1816
Zhang W, Ramamoorthy Y, Kilicarslan T, Nolte H, Tyndale RF, Sellers EM (2002) Inhibition of cytochromes P450 by antifungal imidazole derivatives. Drug Metab Dispos 30:314–318
O’Reilly RA, Goulart DA, Kunze KL, Neal J, Gibaldi M, Eddy AC, Trager WF (1992) Mechanisms of the stereoselective interaction between miconazole and racemic warfarin in human subjects. Clin Pharmacol Ther 51:656–667
Ariyaratnam S, Thakker NS, Sloan P, Thornhill MH (1997) Potentiation of warfarin anticoagulant activity by miconazole oral gel. BMJ 314:349
Pemberton MN, Oliver RJ, Theaker ED (2004) Miconazole oral gel and drug interactions. Br Dent J 196:529–531
Silingardi M, Ghirarduzzi A, Tincani E, Iorio A, Iori I (2000) Miconazole oral gel potentiates warfarin anticoagulant activity. Thromb Haemost 83:794–795
Saari TI, Laine K, Leino K, Valtonen M, Neuvonen PJ, Olkkola KT (2006) Effect of voriconazole on the pharmacokinetics and pharmacodynamics of intravenous and oral midazolam. Clin Pharmacol Ther 79:362–370
Purkins L, Wood N, Kleinermans D, Nichols D (2003) Voriconazole potentiates warfarin-induced prothrombin time prolongation. Br J Clin Pharmacol 56(Suppl 1):24–29
Theuretzbacher U, Ihle F, Derendorf H (2006) Pharmacokinetic/pharmacodynamic profile of voriconazole. Clin Pharmacokinet 45:649–663
Brideau C, Kargman S, Liu S, Dallob AL, Ehrich EW, Rodger IW, Chan CC (1996) A human whole blood assay for clinical evaluation of biochemical efficacy of cyclooxygenase inhibitors. Inflamm Res 45:68–74
Chavez-Eng CM, Constanzer ML, Matuszewski BK (2000) Determination of rofecoxib (MK-0966), a cyclooxygenase-2 inhibitor, in human plasma by high-performance liquid chromatography with tandem mass spectrometric detection. J Chromatogr B Biomed Sci Appl 748:31–39
Gage R, Stopher DA (1998) A rapid HPLC assay for voriconazole in human plasma. J Pharm Biomed Anal 17:1449–1453
Pennick GJ, Clark M, Sutton DA, Rinaldi MG (2003) Development and validation of a high-performance liquid chromatography assay for voriconazole. Antimicrob Agents Chemother 47:2348–2350
Compas D, Touw DJ, de Goede PN (1996) Rapid method for the analysis of itraconazole and hydroxyitraconazole in serum by high-performance liquid chromatography. J Chromatogr B Biomed Appl 687:453–456
Roberts PH, Bersuder P (2006) Analysis of OSPAR priority pharmaceuticals using high-performance liquid chromatography-electrospray ionisation tandem mass spectrometry. J Chromatogr 1134:143–150
Saari TI, Laine K, Leino K, Valtonen M, Neuvonen PJ, Olkkola KT (2006) Voriconazole, but not terbinafine, markedly reduces alfentanil clearance and prolongs its half-life. Clin Pharmacol Ther 80:502–508
Agrawal NG, Matthews CZ, Mazenko RS, Woolf EJ, Porras AG, Chen X, Miller JL, Michiels N, Wehling M, Schultz A, Gottlieb AB, Kraft WK, Greenberg HE, Waldman SA, Curtis SP, Gottesdiener KM (2004) The effects of modifying in vivo cytochrome P450 3A (CYP3A) activity on etoricoxib pharmacokinetics and of etoricoxib administration on CYP3A activity. J Clin Pharmacol 44:1125–1131
Dallob A, Hawkey CJ, Greenberg H, Wight N, De Schepper P, Waldman S, Wong P, DeTora L, Gertz B, Agrawal N, Wagner J, Gottesdiener K (2003) Characterization of etoricoxib, a novel, selective COX-2 inhibitor. J Clin Pharmacol 43:573–585
Andersohn F, Suissa S, Garbe E (2006) Use of first- and second-generation cyclooxygenase-2-selective nonsteroidal antiinflammatory drugs and risk of acute myocardial infarction. Circulation 113:1950–1957
Curtis SP, Ng J, Yu Q, Shingo S, Bergman G, McCormick CL, Reicin AS (2004) Renal effects of etoricoxib and comparator nonsteroidal anti-inflammatory drugs in controlled clinical trials. Clin Ther. 26:70–83
Acknowledgments
This work was supported by Turku University Hospital research fund EVO 13390 (Laine) EVO 13821 (Olkkola). Mr. Tero Vahlberg is thanked for his assistance in statistical issues. Mrs. Elina Kahra is thanked for her skilful assistance in organizing the study.
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Hynninen, V.V., Olkkola, K.T., Neuvonen, P.J. et al. Oral voriconazole and miconazole oral gel produce comparable effects on the pharmacokinetics and pharmacodynamics of etoricoxib. Eur J Clin Pharmacol 65, 89–95 (2009). https://doi.org/10.1007/s00228-008-0556-9
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DOI: https://doi.org/10.1007/s00228-008-0556-9