Lumiracoxib: Pharmacokinetic and Pharmacodynamic Profile When Coadministered with Fluconazole in Healthy Subjects
| Autor: | Slavica Milosavljev, Aziz Laurent, Ching-Ming Yeh, Graham Scott, Linda Yih, Christiane Rordorf |
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| Rok vydání: | 2004 |
| Předmět: |
Adult
Male Antifungal Agents Diclofenac Pharmacology Pharmacokinetics Humans Medicine Cyclooxygenase Inhibitors Drug Interactions Pharmacology (medical) Dosing Organic Chemicals Fluconazole CYP2C9 Cyclooxygenase 2 Inhibitors business.industry Membrane Proteins Crossover study Confidence interval Isoenzymes Thromboxane B2 Cyclooxygenase 2 Prostaglandin-Endoperoxide Synthases Area Under Curve Pharmacodynamics Female Lumiracoxib business medicine.drug |
| Zdroj: | The Journal of Clinical Pharmacology. 44:193-199 |
| ISSN: | 0091-2700 |
| Popis: | 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 B(2) (TxB(2)) 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- infinity ) but had no effect on lumiracoxib mean C(max). The geometric mean ratio (lumiracoxib plus fluconazole/lumiracoxib alone) for AUC(0- infinity ) 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. |
| Databáze: | OpenAIRE |
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