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The cytochrome P450 isoenzyme and some new opportunities for the prediction of negative drug interaction in vivo
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08.05.2018 |
Sychev D.
Ashraf G.
Svistunov A.
Maksimov M.
Tarasov V.
Chubarev V.
Otdelenov V.
Denisenko N.
Barreto G.
Aliev G.
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Drug Design, Development and Therapy |
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8 |
Ссылка
© 2018 Sychev et al. Cytochrome (CYP) 450 isoenzymes are the basic enzymes involved in Phase I biotransformation. The most important role in biotransformation belongs to CYP3A4, CYP2D6, CYP2C9, CYP2C19 and CYP1A2. Inhibition and induction of CYP isoenzymes caused by drugs are important and clinically relevant pharmacokinetic mechanisms of drug interaction. Investigation of the activity of CYP isoenzymes by using phenotyping methods (such as the determination of the concentration of specific substrates and metabolites in biological fluids) during drug administration provides the prediction of negative side effects caused by drug interaction. In clinical practice, the process of phenotyping of CYP isoenzymes and some endogenous substrates in the ratio of cortisol to 6β-hydroxycortisol in urine for the evaluation of CYP3A4 activity has been deemed to be a quite promising, safe and minimally invasive method for patients nowadays.
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Prolongation of the qt interval in patients with coronary heart disease as consequence of drug-drug interactions on metabolic rate
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01.01.2018 |
Ismagilov A.
Shikh E.
Sizova Z.
Shindryaeva N.
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Electronic Journal of General Medicine |
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0 |
Ссылка
© 2018 by the authors; licensee Modestum Ltd., UK. Objective: Prolongation of the QT interval in patients with coronary heart disease (CAD) is a risk factor of polymorphic ventricular tachycardia (PVT) and as consequence, the sudden death. Drug-drug interactions (DDI) on metabolic rate involving cytochrome P-450 (CYP) is the one of the major cause of Long QT Syndrome (LQTS). The aim of the present study was to improve the safety of combined pharmacotherapy when using drugs that affect the QT interval. Method and Results: Medication occurrence of potential dangerous combination of medicines that are affected on QT interval duration in patients with CAD are researched (outpatient medical records (patient history) analysis). Clinical relevance of DDI, which are associated with changes in CYP enzyme activity, categorized by drugs.com Medication Guide. Finding potential dangerous combination of medicines that are affected on QT interval duration were administered to patients with CAD in 3.6% cases in outpatient clinical practice. The most often prescribed combination of drugs is amiodarone and torasemide (13.3% evidence of all concomitant administration that are leading to QT prolongation). The potential mechanism of Amiodarone and Torasemide interaction on metabolic rate that are leading to QT prolongation are competitive substrates CYP 2C8 and a result of inhibited CYP 2C9 by amiodarone. Conclusion: Ability to predict the prolongation of the QT interval caused by DDI on metabolic rate make possible to improve the safety concomitant administration to patients with CAD.
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The individual tailoring of immunosuppressive therapy after heart transplantation
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01.01.2018 |
Koloskova N.
Poptsov V.
Shevchenko A.
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Vestnik Transplantologii i Iskusstvennykh Organov |
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0 |
Ссылка
© 2018 Russian Transplant Society. All rights reserved. Heart transplantation is the gold standard of treatment severe heart failure. Immunosuppressive therapy aimed at the prevention of acute allograft rejection is the cornerstone of post-transplant management. In addition to its direct effects, immunosuppressive therapy is also involved in the generation of a number of post-transplant morbidities that limit the long-term outcome of heart transplant recipients. Given these data it appears that the individual tailoring of immunosuppressive therapy is of paramount importance in determining the outcome of heart transplantation. The goal of immunosuppressive therapy is to prevent rejection of the transplanted heart, while minimizing drug-related effects, such as infection, malignancy, diabetes, hypertension, and renal insuffi ciency. This review aimed is to analyze the protocols for the appointment of immunosuppressive therapy in various groups of recipients after heart transplantation.
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