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Lumiracoxib: Pharmacokinetic and Pharmacodynamic Profile When Coadministered with Fluconazole in Healthy Subjects
Author(s) -
Scott Graham,
Yih Linda,
Yeh ChingMing,
Milosavljev Slavica,
Laurent Aziz,
Rordorf Christiane
Publication year - 2004
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270003262110
Subject(s) - fluconazole , pharmacokinetics , medicine , crossover study , pharmacology , pharmacodynamics , drug interaction , placebo , antifungal , alternative medicine , pathology , dermatology
This two‐way crossover study evaluated the effect of fluconazole on the pharmacokinetics and selective COX‐2 inhibition of lumiracoxib. Thirteen healthy subjects were randomized to fluconazole (day 1: 400 mg; days 2–4: 200 mg) or no drug. On day 4, all subjects received a single dose of lumiracoxib (400 mg). Lumiracoxib pharmacokinetics were assessed during the following 48 hours. Thromboxane B2 (TxB2) inhibition was measured prior to lumiracoxib dosing and 2 hours afterwards. Fluconazole caused a small (18%) but not clinically relevant increase in lumiracoxib mean AUC 0‐∞ but had no effect on lumiracoxib mean C max . The geometric mean ratio (lumiracoxib plus fluconazole/ lumiracoxib alone) for AUC 0‐∞ was 1.19 (90% confidence interval [CI] = 1.12, 1.27) and for C max was 1.11 (90% CI = 0.98, 1.27). The decrease in TxB 2 from predose was not significantly different for lumiracoxib (11.8%) or lumiracoxib plus fluconazole (7.1%); no correlation between lumiracoxib concentration and TxB 2 decrease was seen. As fluconazole is a strong inhibitor of cytochrome P450 (CYP) 2C9, other CYP2C9 inhibitors are unlikely to affect lumiracoxib pharmacokinetics with clinical relevance, making dosage adjustment unnecessary.