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Clinical Pharmacokinetics

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01.11.2008 | Review Article

Clinical Pharmacokinetic and Pharmacodynamic Profile of Etoricoxib

verfasst von: Jody K. Takemoto, Jonathan K. Reynolds, Connie M. Remsberg, Karina R. Vega-Villa, Dr Neal M. Davies

Erschienen in: Clinical Pharmacokinetics | Ausgabe 11/2008

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Abstract

The NSAID etoricoxib is a selective inhibitor of cyclo-oxygenase 2 (COX-2), approved for treatment of patients with chronic arthropathies and musculoskeletal and dental pain. The rate of absorption of etoricoxib is moderate when given orally (the maximum plasma drug concentration occurs after ∼1 hour), and the extent of absorption is similar with oral and intravenous doses. Etoricoxib is extensively protein bound, primarily to plasma albumin, and has an apparent volume of distribution of 120 L in humans. The area under the plasma concentration-time curve (AUC) of etoricoxib increases in proportion to increasing oral doses between 5 and 120 mg. The elimination half-life of ∼20 hours in healthy subjects enables once-daily dosing. Etoricoxib is eliminated following biotransformation to carboxylic acid and glucuronide metabolites that are excreted in urine and faeces, with little of the drug (<1%) being eliminated unchanged in the urine. Etoricoxib is metabolized primarily by the cytochrome P450 (CYP) 3A4 isoenzyme. Plasma concentrations (AUC) of etoricoxib appear not to be different in patients with chronic renal insufficiency compared with individuals who have normal renal function. Compared with healthy subjects, it has been reported that the AUC is increased by approximately 40% in patients with moderate hepatic impairment. No inhibitory effects on CYP2C9, 2C19, 2D6, 2E1 or 3A4 are expected to occur with etoricoxib. Coadministration of etoricoxib with other drugs has been examined only to a limited extent, thus further assessment is necessary. Etoricoxib has been assessed for the management of several specific disease states, including pain, osteoarthritis, and rheumatoid arthritis, and has shown similar efficacy in comparison with traditional NSAIDs (including naproxen, diclofenac and ibuprofen) in these conditions. Etoricoxib has demonstrated a significant reduction in gastrointestinal toxicity compared with many traditional NSAIDs. The renal adverse effects of etoricoxib appear to be similar to those of other NSAIDs, and the cardiovascular adverse effects of this selective COX-2 inhibitor require further clinical scrutiny. Further study is necessary to delineate the relevance of the pharmacokinetic disposition in terms of the clinical benefits and risks of etoricoxib compared with other options in the clinical arsenal.

The use of trade names is for product identification purposes only and does not imply endorsement.

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Titel: Clinical Pharmacokinetic and Pharmacodynamic Profile of Etoricoxib
verfasst von: Jody K. Takemoto
Jonathan K. Reynolds
Connie M. Remsberg
Karina R. Vega-Villa
Dr Neal M. Davies
Publikationsdatum: 01.11.2008
Verlag: Springer International Publishing
Erschienen in: Clinical Pharmacokinetics / Ausgabe 11/2008
Print ISSN: 0312-5963
Elektronische ISSN: 1179-1926
DOI: https://doi.org/10.2165/00003088-200847110-00002

Springer Medizin

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