Acyclic nucleoside phosphonates: a study on cytochrome P450 gene expression
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- Keywords
- Adefovir, CYP, PMEA, PMPA, antiviral, drug metabolism, induction, tenofovir,
- MeSH
- Adenine analogs & derivatives metabolism MeSH
- Real-Time Polymerase Chain Reaction MeSH
- Mice, Inbred C57BL MeSH
- Organophosphonates chemistry metabolism MeSH
- Gene Expression Regulation, Enzymologic * MeSH
- Oligonucleotide Array Sequence Analysis MeSH
- Gene Expression Profiling MeSH
- Cytochrome P-450 Enzyme System genetics metabolism MeSH
- Tenofovir MeSH
- Blotting, Western MeSH
- Animals MeSH
- Check Tag
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- adefovir dipivoxil MeSH Browser
- Adenine MeSH
- Organophosphonates MeSH
- Cytochrome P-450 Enzyme System MeSH
- Tenofovir MeSH
1. Nucleotide analogues comprise an important class of drugs used in treatment of viral infections but also cancer. These drugs affect the structural integrity of DNA and activate different pathways and processes in the cell and may directly or indirectly influence the drug metabolizing system. Adefovir dipivoxil (AD) and tenofovir disoproxil (TD) are nucleotide analogues approved for the treatment of chronic hepatitis B and/or HIV/AIDS infection. 2. To evaluate the risk of their drug-drug interactions on the level of drug metabolism, an effect of both compounds on cytochromes P450 expression was studied using cDNA microarrays, real-time RT-PCR and immunoblotting. Mice were given intraperitoneally 25 mg/kg of AD or TD, respectively. As a positive control, a combination of prototypic cytochromes P450 (CYP) inducers, phenobarbital and β-naphthoflavone was chosen. 3. The data obtained showed a significant CYP induction in the positive control group, but no clinically significant induction of CYP genes by AD or TD was observed. Our results support the evidence of safety of AD and TD with respect to drug-drug interactions based on enzyme induction. These findings are important as a plethora of new antivirals of different types are being tested and introduced to clinical practice, mostly to be used in combinations.
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