Effects of artemisinin antimalarials on Cytochrome P450 enzymes in vitro using recombinant enzymes and human liver microsomes: potential implications for combination therapies.

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Ericsson T, Sundell J, Torkelsson A, Hoffmann KJ, Ashton M

Effects of artemisinin antimalarials on Cytochrome P450 enzymes in vitro using recombinant enzymes and human liver microsomes: potential implications for combination therapies.

Xenobiotica. 2014 Jul;44(7):615-26. doi: 10.3109/00498254.2013.878815. Epub 2014 Jan 8.

PubMed ID

24400699 [ View in PubMed

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Abstract

1. Cytochrome P450 enzyme system is the most important contributor to oxidative metabolism of drugs. Modification, and more specifically inhibition, of this system is an important determinant of several drug-drug interactions (DDIs). 2. Effects of the antimalarial agent artemisinin and its structural analogues, artemether, artesunate and dihydroartemisinin, on seven of the major human liver CYP isoforms (CYP1A2, 2A6, 2B6, 2C9, 2C19, 2D6 and 3A4) were evaluated using recombinant enzymes (fluorometric assay) and human liver microsomes (LC-MS/MS analysis). Inhibitory potency (IC50) and mechanisms of inhibition were evaluated using nonlinear regression analysis. In vitro-in vivo extrapolation using the [I]/Ki ratio was applied to predict the risk of DDI in vivo. 3. All compounds tested inhibited the enzymatic activity of CYPs, mostly through a mixed type of inhibition, with CYP1A2, 2B6, 2C19 and 3A4 being affected. A high risk of interaction in vivo was predicted if artemisinin is coadministrated with CYP1A2 or 2C19 substrates. 4. With respect to CYP1A2 inhibition in vivo by artemisinin compounds, our findings are in line with previously published data. However, reported risks of interaction may be overpredicted and should be interpreted with caution.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Artenimol	Cytochrome P450 2C19	Protein	Humans	Unknown	Inhibitor	Details

Drug Interactions

Drugs	Interaction
Integrate drug-drug interactions in your software
Amodiaquine Vemurafenib	The risk or severity of QTc prolongation can be increased when Vemurafenib is combined with Amodiaquine.
Artemether Vemurafenib	The risk or severity of QTc prolongation can be increased when Vemurafenib is combined with Artemether.
Artemotil Vemurafenib	The risk or severity of QTc prolongation can be increased when Vemurafenib is combined with Artemotil.
Artenimol Vemurafenib	The risk or severity of QTc prolongation can be increased when Vemurafenib is combined with Artenimol.
Artesunate Vemurafenib	The risk or severity of QTc prolongation can be increased when Vemurafenib is combined with Artesunate.