Tamoxifen pharmacokinetics

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    Tamoxifen pharmacokinetics


    Received date: June 14, 2016; Accepted date: June 20, 2016; Published date: June 24, 2016 Citation: Ibrahim N (2016) Integrating Personalization of Treatment with Tamoxifen into Pharmacy Practice Via Clinical Pharmacist Role in Therapy Management. doi:10.4172/2376-0419.1000162 Copyright: © 2016 Ibrahim N. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Visit for more related articles at Journal of Pharmaceutical Care & Health Systems The concept of individualized therapy is intended to deliver the right therapy to the right patient at the right time. Personalization of treatment aims to shift health care from population based or empirical approach to scientifically tailored approach. Pharmacogenenetics use the genetic information such as DNA sequence, gene expression and copy number to explain the inter-individual differences in drug metabolism (pharmacokinetics) and physiological drug response (pharmacodynamics), to predict the efficacy and toxicity of drugs and to identify responders and non responders to a specific drug. Success of the personalized medicine depends on the identification of predictive biomarkers and development of accurate and reliable diagnostics. It is the corner stone therapy for breast cancer either in the adjuvant or metastatic setting mainly in patients with female hormone receptors positivity. Response to tamoxifen is affected by the genetic variation of CYP2D6. This cytochrome is responsible for tamoxifen metabolism to its active metabolite endoxifen. The antiestrogenic drug tamoxifen is widely used in the treatment of estrogen receptor-α-positive breast cancer and substantially decreases recurrence and mortality rates. However, high interindividual variability in response is observed, calling for a personalized approach to tamoxifen treatment. Tamoxifen is bioactivated by cytochrome P450 (CYP) enzymes such as CYP2B6, CYP2C9, CYP2C19, CYP2D6 and CYP3A4/5, resulting in the formation of active metabolites, including 4-hydroxy-tamoxifen and…

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    This model is able to simulate the pharmacokinetics PK after single and repeated oral tamoxifen doses in female breast cancer patients in dependence of the. Feb 2, 1990. pharmacokinetics of tamoxifen in animal models used to study tamoxifen action have not been investi- gated, although metabolism obviously. Abstract The anti-estrogen tamoxifen is characterized by a large variability in response, partly due to pharmacokinetic differences. We examined circadian.

    ) mammary carcinoma and applied to breast cancer patients all over the world. Endoxifen is a secondary and highly active metabolite of tamoxifen that is formed among others by the polymorphic cytochrome P450 2D6 (CYP2D6). It is widely accepted that CYP2D6 poor metabolizers exert a pronounced decrease in endoxifen steady-state plasma concentrations compared to CYP2D6 extensive metabolizers. Nevertheless, an in-depth understanding of the chain of cause and effect between CYP2D6 genotype, endoxifen steady-state plasma concentration, and subsequent tamoxifen treatment benefit still remains to be evolved. In this study, physiologically based pharmacokinetic (PBPK)-modeling was applied to mechanistically investigate the impact of CYP2D6 phenotype on endoxifen formation in female breast cancer patients undergoing tamoxifen therapy. A PBPK-model of tamoxifen and its pharmacologically important metabolites N-desmethyltamoxifen (NDM-TAM), 4-hydroxytamoxifen (4-OH-TAM), and endoxifen was developed and validated. This model is able to simulate the pharmacokinetics (PK) after single and repeated oral tamoxifen doses in female breast cancer patients in dependence of the CYP2D6 phenotype. In 2006, the large STAR clinical study concluded that raloxifene is equally effective in reducing the incidence of breast cancer, but after an average 4-year follow-up, although the difference was not statistically significant, there were 36% fewer uterine cancers and 29% fewer blood clots in women taking raloxifene than in women taking tamoxifen. Tamoxifen improves fertility in males with infertility by disinhibiting the hypothalamic–pituitary–gonadal axis (HPG axis) via ER antagonism and thereby increasing the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and increasing testicular testosterone production. It is taken as a preventative measure in small doses, or used at the onset of any symptoms such as nipple soreness or sensitivity. Other drugs are taken for similar purposes such as clomifene and the anti-aromatase drugs which are used in order to try to avoid the hormone-related adverse effects. Occasionally tamoxifen is used in treatment of the rare conditions of retroperitoneal fibrosis A report in September 2009 from Health and Human Services' Agency for Healthcare Research and Quality suggests that tamoxifen, raloxifene, and tibolone used to treat breast cancer significantly reduce invasive breast cancer in midlife and older women, but also increase the risk of adverse side effects. Some cases of lower-limb lymphedema have been associated with the use of tamoxifen, due to the blood clots and deep vein thrombosis (DVT) that can be caused by this medication. Resolution of the blood clots or DVT is needed before lymphedema treatment can be initiated.

    Tamoxifen pharmacokinetics

    PharmGKB, Metabolites, pharmacodynamics, and pharmacokinetics of tamoxifen.

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  7. TAMOXIFEN PHARMACOKINETICS PATHWAY PW0000838. View Ontology Report. Description. Tamoxifen TAM, TX, an non-steroidal anti-estrogen, is one.

    • Tamoxifen pharmacokinetics pathwayRat Genome Database.
    • Circadian variation in tamoxifen pharmacokinetics in mice and breast..
    • Effects of Pharmacogenetics on the Pharmacokinetics and..

    Nov 4, 2015. 15 days pre-treatment with red clover did not alter the tamoxifen and its active metabolite 4-hydroxytamoxifen pharmacokinetics significantly p. Dec 26, 2016. Tamoxifen pharmacokinetics. Absorption and distribution Tamoxifen is available as 10mg tablet and administered as 20mg once daily. PharmacoKINEtics of TAMoxifen and Its Metabolites in Breast Cancer Patients the Influence of a Dose Increase in Phenotypic Poor Metabolizers of CYP2D6 KINETAM.

     
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