Geneva cocktail for cytochrome p450 and P-glycoprotein activity assessment using dried blood spots.

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State: Serval
Version: Final published version
Serval ID
serval:BIB_94BFF516FD92
Type
Article: article from journal or magazin.
Collection
Publications
Title
Geneva cocktail for cytochrome p450 and P-glycoprotein activity assessment using dried blood spots.
Journal
Clinical Pharmacology and Therapeutics
Author(s)
Bosilkovska M., Samer C.F., Déglon J., Rebsamen M., Staub C., Dayer P., Walder B., Desmeules J.A., Daali Y.
ISSN
1532-6535 (Electronic)
ISSN-L
0009-9236
Publication state
Published
Issued date
2014
Peer-reviewed
Oui
Volume
96
Number
3
Pages
349-359
Language
english
Notes
Publication types: Evaluation Studies ; Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Abstract
The suitability of the capillary dried blood spot (DBS) sampling method was assessed for simultaneous phenotyping of cytochrome P450 (CYP) enzymes and P-glycoprotein (P-gp) using a cocktail approach. Ten volunteers received an oral cocktail capsule containing low doses of the probes bupropion (CYP2B6), flurbiprofen (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), midazolam (CYP3A), and fexofenadine (P-gp) with coffee/Coke (CYP1A2) on four occasions. They received the cocktail alone (session 1), and with the CYP inhibitors fluvoxamine and voriconazole (session 2) and quinidine (session 3). In session 4, subjects received the cocktail after a 7-day pretreatment with the inducer rifampicin. The concentrations of probes/metabolites were determined in DBS and plasma using a single liquid chromatography-tandem mass spectrometry method. The pharmacokinetic profiles of the drugs were comparable in DBS and plasma. Important modulation of CYP and P-gp activities was observed in the presence of inhibitors and the inducer. Minimally invasive one- and three-point (at 2, 3, and 6 h) DBS-sampling methods were found to reliably reflect CYP and P-gp activities at each session.
Keywords
Administration, Oral, Adult, Bupropion/administration & dosage, Bupropion/blood, Caffeine/administration & dosage, Caffeine/blood, Capsules, Carbonated Beverages, Chromatography, High Pressure Liquid, Chromatography, Reverse-Phase, Coffee, Cytochrome P-450 Enzyme System/antagonists & inhibitors, Cytochrome P-450 Enzyme System/blood, Dextromethorphan/administration & dosage, Dextromethorphan/blood, Dried Blood Spot Testing, Enzyme Inhibitors/administration & dosage, Feasibility Studies, Flurbiprofen/administration & dosage, Flurbiprofen/blood, Humans, Isoenzymes, Male, Midazolam/administration & dosage, Midazolam/blood, Omeprazole/administration & dosage, Omeprazole/blood, P-Glycoprotein/antagonists & inhibitors, P-Glycoprotein/blood, Pharmaceutical Preparations/administration & dosage, Pharmaceutical Preparations/blood, Phenotype, Pilot Projects, Predictive Value of Tests, Spectrometry, Mass, Electrospray Ionization, Substrate Specificity, Tandem Mass Spectrometry, Terfenadine/administration & dosage, Terfenadine/analogs & derivatives, Young Adult
Pubmed
Web of science
Create date
08/12/2014 18:05
Last modification date
03/03/2018 19:38
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