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- Title
Incorporation of Flurbiprofen in a 4-Drug Cytochrome P450 Phenotyping Cocktail.
- Authors
Bosilkovska, Marija; Clément, Mallorie; Dayer, Pierre; Desmeules, Jules; Daali, Youssef
- Abstract
Cytochromes P450 (CYP) constitute the major drug-metabolizing enzyme system in human beings. The activity of these enzymes is subjected to a great interindividual variability which can cause interindividual differences in plasma drug concentrations and result in therapeutic failure or side effects. To avoid these problems, it is of great importance to evaluate the in vivo CYP activity (phenotyping). In the beginning of the 1990s, a 'cocktail' approach was developed, aiming to simultaneously assess the activity of multiple CYPs by the administration of a cocktail of CYP-specific probe drugs [1]. Several cocktails using different probe drugs have been developed in the past years [2-7]. Few of these cocktails use wellvalidated probes such as caffeine, omeprazole, dextromethorphan and midazolam for the phenotyping of CYP1A2, CYP2C19, CYP2D6 and CYP3A, respectively [2,4,5]. These drugs have no mutual interactions as previously demonstrated [5]. Two of these cocktails also include losartan [4] or warfarin [2] as probes for CYP2C9 activity. These drugs, as well as tolbutamide [8] and phenytoin [9], have been proposed as potentially useful CYP2C9 probes. However, all of the proposed CYP2C9 substrates are associated with limitations which make them less than ideal as probes for this enzyme [10]. Recently, flurbiprofen has been validated as a reliable probe for CYP2C9 phenotyping both in urine [10] and single point plasma samples [11]. Flurbiprofen has also been incorporated in the Pittsburgh cocktail and was shown not to interact with the other probes. [7]. In this study, we aimed to validate the incorporation of flurbiprofen as a CYP2C9 probe to a cocktail composed of caffeine, omeprazole, dextromethorphan and midazolam and verify the effect these drugs have on flurbiprofen metabolic ratio.
- Subjects
CYTOCHROME P-450; PHENOTYPES; FLURBIPROFEN; DRUG metabolism; MIDAZOLAM
- Publication
Basic & Clinical Pharmacology & Toxicology, 2014, Vol 115, Issue 5, p465
- ISSN
1742-7835
- Publication type
Article
- DOI
10.1111/bcpt.12231