HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:
Sign In to gain access to subscriptions and/or personal tools.

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Request Reprints Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (11) Citing Articles via Google Scholar Google Scholar Articles by Scott, G. Articles by Rordorf, C. Search for Related Content PubMed PubMed Citation Articles by Scott, G. Articles by Rordorf, C. Social Bookmarking                         What's this?

Lumiracoxib: Pharmacokinetic and Pharmacodynamic Profile When Coadministered with Fluconazole in Healthy Subjects

From the Department of Exploratory Clinical Development, Novartis Pharmaceuticals, Horsham, United Kingdom (Dr. Scott); Departments of Exploratory Clinical Development, Biostatistics, and Bioanalytics, Novartis Pharmaceuticals, East Hanover, New Jersey (L. Yih, Dr. Yeh, S. Milosavljev); PPD Development, Austin, Texas (Dr. Laurent); and Department of Exploratory Clinical Development, Novartis Pharmaceuticals, Basel, Switzerland (Dr. Rordorf).

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 TxB₂ from predose was not significantly different for lumiracoxib (11.8%) or lumiracoxib plus fluconazole (7.1%); no correlation between lumiracoxib concentration and TxB₂ 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.

Key Words: Lumiracoxib • fluconazole • drug interactions • COX-2 inhibitors • pharmacokinetics

Address for reprints: Christiane Rordorf, MD, Department of Exploratory Clinical Development, Novartis Pharma AG, WSJ 210-313, CH-4002, Basel, Switzerland.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				S. J. Gardiner and E. J. Begg Pharmacogenetics, Drug-Metabolizing Enzymes, and Clinical Practice Pharmacol. Rev., September 1, 2006; 58(3): 521 - 590. [Abstract] [Full Text] [PDF]

				V.-V. Hynninen, K. T. Olkkola, K. Leino, S. Lundgren, P. J. Neuvonen, A. Rane, M. Valtonen, H. Vyyrylainen, and K. Laine Effects of the antifungals voriconazole and fluconazole on the pharmacokinetics of s-(+)- and R-(-)-Ibuprofen. Antimicrob. Agents Chemother., June 1, 2006; 50(6): 1967 - 1972. [Abstract] [Full Text] [PDF]

				A. D. Rodrigues IMPACT OF CYP2C9 GENOTYPE ON PHARMACOKINETICS: ARE ALL CYCLOOXYGENASE INHIBITORS THE SAME? Drug Metab. Dispos., November 1, 2005; 33(11): 1567 - 1575. [Abstract] [Full Text] [PDF]