Geneva Cocktail for Cytochrome P450 and P-glycoprotein Activity Assessment Using Dried Blood Spots

Bosilkovska Weisskopf, Marija; Samer, Caroline Flora; Deglon, Julien; Rebsamen, Michela; Staub, Christian; Dayer, Pierre; Walder, Bernhard; Desmeules, Jules Alexandre; Daali, Youssef

doi:10.1038/clpt.2014.83

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Title		Geneva Cocktail for Cytochrome P450 and P-glycoprotein Activity Assessment Using Dried Blood Spots
Authors		Bosilkovska Weisskopf, Marija Samer, Caroline Flora Deglon, Julien Rebsamen, Michela Staub, Christian Dayer, Pierre Walder, Bernhard Desmeules, Jules Alexandre Daali, Youssef show all authors [1 - 9]
Published in		Clinical pharmacology and therapeutics. 2014, vol. 96, no. 3, p. 349-359
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.Clinical Pharmacology & Therapeutics (2014); advance online publication 7 May 2014. doi:10.1038/clpt.2014.83.
Identifiers		DOI: 10.1038/clpt.2014.83 PMID: 24722393
Full text		Article (Published version) (822 Kb) - Free access
Structures		Faculté de médecine / Section de médecine clinique / Département d'anesthésiologie, pharmacologie, soins intensifs et urgences Faculté de médecine / Section de médecine fondamentale / Département de biologie structurale et bioinformatique Faculté de médecine / Section de médecine clinique / Département de santé et médecine communautaires / Institut de médecine légale
Research groups		Groupe Desmeules Jules (pharmacologie/toxicologie) (567) Pharmaco-omiques et médecine de précision (1003)
Citation (ISO format)		BOSILKOVSKA WEISSKOPF, Marija et al. Geneva Cocktail for Cytochrome P450 and P-glycoprotein Activity Assessment Using Dried Blood Spots. In: Clinical pharmacology and therapeutics, 2014, vol. 96, n° 3, p. 349-359. doi: 10.1038/clpt.2014.83 https://archive-ouverte.unige.ch/unige:36848