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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    Abstract The anti-estrogen tamoxifen is characterized by a large variability in response, partly due to pharmacokinetic differences. We examined circadian. 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. Tamoxifen Citrate Pharmacokinetics Absorption Bioavailability. Absorbed slowly following oral administration; peak serum concentrations of tamoxifen occur.

    ) 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, Physiologically-based pharmacokinetic modeling of tamoxifen and its.

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  6. Dec 26, 2016. Tamoxifen pharmacokinetics. Absorption and distribution Tamoxifen is available as 10mg tablet and administered as 20mg once daily.

    • Integrating Personalization of Treatment with Tamoxifen into..
    • Tamoxifen Citrate Monograph for Professionals -.
    • Tamoxifen - Wikipedia.

    TAMOXIFEN PHARMACOKINETICS PATHWAY PW0000838. View Ontology Report. Description. Tamoxifen TAM, TX, an non-steroidal anti-estrogen, is one. May 5, 2015. To tailor tamoxifen treatment, multiple studies have been performed to clarify the influence of polymorphisms on its pharmacokinetics and. Tamoxifen Pharmacokinetics Beyond the Genotyping Era. ISBN 9-054-8. Lay-out and cover Design Roderick van Klink. Printed by Ridderprint B. V.

     
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    Sertraline is used for a number of conditions, including major depressive disorder (MDD), obsessive–compulsive disorder (OCD), body dysmorphic disorder (BDD), posttraumatic stress disorder (PTSD), premenstrual dysphoric disorder (PMDD), panic disorder, and social anxiety disorder (SAD). The comparative efficacy of sertraline and TCAs for melancholic depression has not been studied. A 1998 review suggested that, due to its pharmacology, sertraline may be more efficacious than other SSRIs and equal to TCAs for the treatment of melancholic depression. A meta-analysis of 12 new-generation antidepressants showed that sertraline and escitalopram are the best in terms of efficacy and acceptability in the acute-phase treatment of adults with unipolar MDD. Sertraline used for the treatment of depression in elderly (older than 60) patients was superior to placebo and comparable to another SSRI fluoxetine, and TCAs amitriptyline, nortriptyline (Pamelor) and imipramine. Sertraline had much lower rates of adverse effects than these TCAs, with the exception of nausea, which occurred more frequently with sertraline. In addition, sertraline appeared to be more effective than fluoxetine or nortriptyline in the older-than-70 subgroup. placebo in elderly patients showed a statistically significant (that is, unlikely to occur by chance), but clinically very modest improvement in depression and no improvement in quality of life. A meta-analysis on SSRIs and SNRIs that look at partial response (defined as at least a 50% reduction in depression score from baseline) found that sertraline, paroxetine and duloxetine were better than placebo. Sertraline an antidepressant - NHS Sertraline - dose, children, effects, therapy, drug, people, used, brain Sertraline - Side Effects, Uses, Dosage, Overdose, Pregnancy, Alcohol.
     
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