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Development and clinical validation of a low-dose phenotyping cocktail for cytochrome P450 and P-glycoprotein activity assessment using dried blood spots

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Defense Thèse de doctorat : Univ. Genève, 2015 - Sc. 4881 - 2015/12/22
Abstract Drug metabolizing enzymes, such as cytochromes P450, and transporters, such as P-glycoprotein, play a crucial role in drug disposition. Their activity is subject to great interindividual variability which can cause differences in drug concentrations and result in therapeutic failure or side effects. In this thesis, a cocktail approach allowing for simultaneous assessment of the in vivo activity of these proteins has been developed. In a first step, an LC/MS-MS method for the quantification of the cocktail probes and their metabolites in DBS has been developed and validated. A first clinical study showed that modulation of cytochromes and P-glycoprotein activities can be reliably predicted using this approach. A second clinical study was performed in order to verify the interaction potential between the probe drugs within the cocktail and thus fully validate the latter. Few clinical study and clinical practice examples of the utility and application of this approach are also presented.
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URN: urn:nbn:ch:unige-800138
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BOSILKOVSKA WEISSKOPF, Marija. Development and clinical validation of a low-dose phenotyping cocktail for cytochrome P450 and P-glycoprotein activity assessment using dried blood spots. Université de Genève. Thèse, 2015. https://archive-ouverte.unige.ch/unige:80013

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Deposited on : 2016-01-25

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