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Clinical Pharmacokinetics
Erschienen in: Clinical Pharmacokinetics 10/2018

17.04.2018 | Systematic Review

Complex Drug–Drug–Gene–Disease Interactions Involving Cytochromes P450: Systematic Review of Published Case Reports and Clinical Perspectives

verfasst von: Flavia Storelli, Caroline Samer, Jean-Luc Reny, Jules Desmeules, Youssef Daali

Erschienen in: Clinical Pharmacokinetics | Ausgabe 10/2018

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Abstract

Drug pharmacokinetics (PK) is influenced by multiple intrinsic and extrinsic factors, among which concomitant medications are responsible for drug–drug interactions (DDIs) that may have a clinical relevance, resulting in adverse drug reactions or reduced efficacy. The addition of intrinsic factors affecting cytochromes P450 (CYPs) activity and/or expression, such as genetic polymorphisms and diseases, may potentiate the impact and clinical relevance of DDIs. In addition, greater variability in drug levels and exposures has been observed when such intrinsic factors are present in addition to concomitant medications perpetrating DDIs. This variability results in poor predictability of DDIs and potentially dramatic clinical consequences. The present review illustrates the issue of complex DDIs using systematically searched published case reports of DDIs involving genetic polymorphisms, renal impairment, cirrhosis, and/or inflammation. Current knowledge on the impact of each of these factors on drug exposure and DDIs is summarized and future perspectives for the management of such complex DDIs in clinical practice are discussed, including the use of advanced Computerized Physician Order Entry (CPOE) systems, the development of model-based dose optimization strategies, and the education of healthcare professionals with respect to personalized medicine.
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Metadaten
Titel
Complex Drug–Drug–Gene–Disease Interactions Involving Cytochromes P450: Systematic Review of Published Case Reports and Clinical Perspectives
verfasst von
Flavia Storelli
Caroline Samer
Jean-Luc Reny
Jules Desmeules
Youssef Daali
Publikationsdatum
17.04.2018
Verlag
Springer International Publishing
Erschienen in
Clinical Pharmacokinetics / Ausgabe 10/2018
Print ISSN: 0312-5963
Elektronische ISSN: 1179-1926
DOI
https://doi.org/10.1007/s40262-018-0650-9

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