ArticleDrug metabolism and disposition: the biological fate of chemicals2011
In vitro cytochrome P450-mediated metabolism of exemestane.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 74 citations in OpenAlex.
- Microplastics as Vectors Influencing Oxidative Stress, Inflammation, and Endocrine Function During Early Development.International journal of molecular sciences · 2026Review
- Impact of combined UGT2B17 and GSTA1 genotypes on exemestane pharmacogenetics.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Determination and Disposition of the Aromatase Inhibitor Exemestane in CYP3A-Deficient Mice.Molecules (Basel, Switzerland) · 2025Article
- Breaking the Barriers of Therapy Resistance: Harnessing Ferroptosis for Effective Hepatocellular Carcinoma Therapy.Journal of hepatocellular carcinoma · 2024Review
- Influence of Glutathione-S-Transferase A1*B Allele on the Metabolism of the Aromatase Inhibitor, Exemestane, in Human Liver Cytosols and in Patients Treated With Exemestane.The Journal of pharmacology and experimental therapeutics · 2022Article
- Article
- Characterization of Cytosolic GlutathioneDrug metabolism and disposition: the biological fate of chemicals · 2021Article
- Identification and Quantification of Novel Major Metabolites of the Steroidal Aromatase Inhibitor, Exemestane.Drug metabolism and disposition: the biological fate of chemicals · 2018Article
- A Novel Multiplex PCR-RFLP Method for Simultaneous Genotyping ofThe Malaysian journal of medical sciences : MJMS · 2018Article
- Role of the UGT2B17 deletion in exemestane pharmacogenetics.The pharmacogenomics journal · 2018Article
- Effects of Honokiol on CYP450 Activity and Transporter mRNA Expression in Type 2 Diabetic Rats.International journal of molecular sciences · 2018Article
- Polymorphisms in drug-metabolizing enzymes and steady-state exemestane concentration in postmenopausal patients with breast cancer.The pharmacogenomics journal · 2017Article
- Impact of the OATP1B1 c.521T>C single nucleotide polymorphism on the pharmacokinetics of exemestane in healthy post-menopausal female volunteers.Journal of clinical pharmacy and therapeutics · 2017Article
- In vitro metabolism of exemestane by hepatic cytochrome P450s: impact of nonsynonymous polymorphisms on formation of the active metabolite 17Pharmacology research & perspectives · 2017Article
- Exemestane potency is unchanged by common nonsynonymous polymorphisms in CYP19A1: results of a novel anti-aromatase activity assay examining exemestane and its derivatives.Pharmacology research & perspectives · 2017Article
- Germline genetic predictors of aromatase inhibitor concentrations, estrogen suppression and drug efficacy and toxicity in breast cancer patients.Pharmacogenomics · 2017Review
- Impact of nonsynonymous single nucleotide polymorphisms on in-vitro metabolism of exemestane by hepatic cytosolic reductases.Pharmacogenetics and genomics · 2016Article
- Impacts of smoking on endocrine treatment response in a prospective breast cancer cohort.British journal of cancer · 2016Article
- Impact of UGT2B17 Gene Deletion on the Pharmacokinetics of 17-Hydroexemestane in Healthy Volunteers.Journal of clinical pharmacology · 2016Article
- Recent Progress in the Discovery of Next Generation Inhibitors of Aromatase from the Structure-Function Perspective.Journal of medicinal chemistry · 2016Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Exemestane is a potent and irreversible steroidal aromatase inhibitor drug used for the treatment of estrogen receptor-positive breast cancer. Our aim was to identify and assess the contribution of the specific cytochromes P450 (P450s) responsible for exemestane primary in vitro metabolism. With the use of high-performance liquid chromatography and liquid chromatography-tandem mass spectrometry analytical techniques, 17-hydroexemestane (MI) formation and 6-hydroxymethylexemestane (MII) formation were found to be the predominant exemestane metabolic pathways. In a bank of 15 well characterized human liver microsomes with known P450 isoform-specific activities, the MI formation rate correlated significantly with CYP1A2 (Spearman r = 0.60, p = 0.02) and CYP4A11 (Spearman r = 0.67, p = 0.01) isoform-specific activities, whereas the MII production rate significantly correlated with CYP2B6 (Spearman r = 0.57, p = 0.03) and CYP3A (Spearman r = 0.76, p = 0.005) isoform-specific activities. Recombinant CYP1A1 metabolized exemestane to MI with a catalytic efficiency (Cl(int)) of 150 nl/pmol P450 × min that was at least 3.5-fold higher than those of other P450s investigated. Recombinant CYP3A4 catalyzed MII formation from exemestane with a catalytic efficiency of 840 nl/pmol P450 × min that was at least 4-fold higher than those of other P450s investigated. Among a panel of 10 chemical inhibitors tested, only ketoconazole and troleandomycin (CYP3A-specific chemical inhibitors) significantly inhibited the formation of MII by 45 and 95%, respectively. None of them markedly inhibited the formation of MI. In summary, exemestane seems to be metabolized to MI by multiple P450s that include CYP4A11 and CYP1A1/2, whereas its oxidation to MII is primarily mediated by CYP3A.
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