Mechanisms and Clinical Significance of Pharmacokinetic-Based Drug-Drug Interactions with Drugs Approved by the U.S. Food and Drug Administration in 2017.
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Yu J, Petrie ID, Levy RH, Ragueneau-Majlessi I
Mechanisms and Clinical Significance of Pharmacokinetic-Based Drug-Drug Interactions with Drugs Approved by the U.S. Food and Drug Administration in 2017.
Drug Metab Dispos. 2019 Feb;47(2):135-144. doi: 10.1124/dmd.118.084905. Epub 2018 Nov 15.
- PubMed ID
- 30442649 [ View in PubMed]
- Abstract
Pharmacokinetic-based drug-drug interaction (DDI) data for drugs approved by the U.S. Food and Drug Administration in 2017 (N = 34) were analyzed using the University of Washington Drug Interaction Database. The mechanisms and clinical relevance of these interactions were characterized based on information from new drug application reviews. CYP3A inhibition and induction explained most of the observed drug interactions (new drugs as victims or as perpetrators), and transporters mediated about half of all DDIs, alone or with enzymes. Organic anion transporting polypeptide (OATP)1B1/1B3 played a significant role, mediating more than half of the drug interactions with area under the time-plasma curve (AUC) changes >/=5-fold. As victims, five new drugs were identified as sensitive substrates: abemeciclib, midostaurin, and neratinib for CYP3A and glecaprevir and voxilaprevir for OATP1B1/1B3. As perpetrators, three drugs were considered strong inhibitors: ribociclib for CYP3A, glecaprevir/pibrentasvir for OATP1B1/1B3, and sofosbuvir/velpatasvir/voxilaprevir for OATP1B1/1B3 and breast cancer resistance protein. No strong inducer of enzymes or transporters was identified. DDIs with AUC changes >/=5-fold and almost all DDIs with AUC changes 2- to 5-fold had dose recommendations in their respective drug labels. A small fraction of DDIs with exposure changes <2-fold had a labeling impact, mostly related to drugs with narrow therapeutic indices. As with drugs approved in recent years, all drugs found to be sensitive substrates or strong inhibitors of enzymes or transporters were among oncology or antiviral treatments, suggesting a serious risk of DDIs in these patient populations for whom effective therapy is already complex because of polytherapy.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Deflazacort Cytochrome P450 3A4 Protein Humans NoSubstrateInducerDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareAbemaciclibCimetidine The metabolism of Abemaciclib can be decreased when combined with Cimetidine. AbemaciclibOlaparib The metabolism of Abemaciclib can be decreased when combined with Olaparib. AbemaciclibPazopanib The metabolism of Abemaciclib can be decreased when combined with Pazopanib. AbemaciclibBuprenorphine The metabolism of Abemaciclib can be decreased when combined with Buprenorphine. AbemaciclibDasatinib The metabolism of Abemaciclib can be decreased when combined with Dasatinib.