Oral voriconazole and miconazole oral gel produce comparable effects on the pharmacokinetics and pharmacodynamics of etoricoxib.
OBJECTIVE
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 B(2) generation were followed after ingestion of 60 mg etoricoxib without pretreatment, after topical administration of miconazole oral gel (85 mg x 3, 3 days), or after oral voriconazole (400 mg x 2, 1st day, 200 mg x 2, 2nd day).


RESULTS
Etoricoxib area under the plasma concentration-time curve (AUC(0-00)) and maximum plasma concentration (C(max)) 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.
Hynninen
Ville V
VV
Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Itäinen Pitkäkatu 4B, 20520 Turku, Finland. vilhyn@utu.fi
Olkkola
Klaus T
KT
Neuvonen
Pertti J
PJ
Laine
Kari
K
D000284:Administration, Oral; D000287:Administration, Topical; D000328:Adult; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D001711:Biotransformation / Q000187:drug effects; D018592:Cross-Over Studies; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D000077613:Etoricoxib; D005782:Gels; D006801:Humans; D008297:Male; D008825:Miconazole / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D011725:Pyridines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011743:Pyrimidines / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D013450:Sulfones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013929:Thromboxane B2 / Q000097:blood; D014230:Triazoles / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D065819:Voriconazole; D055815:Young Adult
D000935:Antifungal Agents; D016861:Cyclooxygenase Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D005782:Gels; D011725:Pyridines; D011743:Pyrimidines; D013450:Sulfones; D014230:Triazoles; D013929:Thromboxane B2; D008825:Miconazole; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; D065819:Voriconazole; D000077613:Etoricoxib
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