The Influence of Pharmacogenetics on the Clinical Relevance of Pharmacokinetic Drug–Drug Interactions: Drug–Gene, Drug–Gene–Gene and Drug–Drug–Gene Interactions

Pharmaceuticals

Martina Hahn¹  SibylleC. Roll² 

[1] Klinik für Psychiatrie, Psychosomatik und Psychotherapie des Universitätsklinikums Frankfurt, 60528 Frankfurt, Germany;Klinik für Psychische Gesundheit, Klinikum Frankfurt Höchst, 65929 Frankfurt, Germany;

关键词: drug–drug interactions;    drug–gene interactions;    drug–g–gene interactions;    phenoconversion;    pharmacogenetics;   

DOI  :  10.3390/ph14050487

来源: DOAJ

【 摘 要 】

Drug interactions are a well-known cause of adverse drug events, and drug interaction databases can help the clinician to recognize and avoid such interactions and their adverse events. However, not every interaction leads to an adverse drug event. This is because the clinical relevance of drug–drug interactions also depends on the genetic profile of the patient. If inhibitors or inducers of drug metabolising enzymes (e.g., CYP and UGT) are added to the drug therapy, phenoconcversion can occur. This leads to a genetic phenotype that mismatches the observable phenotype. Drug–drug–gene and drug–gene–gene interactions influence the toxicity and/or ineffectivness of the drug therapy. To date, there have been limited published studies on the impact of genetic variations on drug–drug interactions. This review discusses the current evidence of drug–drug–gene interactions, as well as drug–gene–gene interactions. Phenoconversion is explained, the and methods to calculate the phenotypes are described. Clinical recommendations are given regarding the integratation of the PGx results in the assessment of the relevance of drug interactions in the future.

【 授权许可】

Unknown