Search results for "CYP450"
showing 5 items of 5 documents
Estudio de interacciones farmacocinéticas del efavirenz con fármacos metabolizados por el CYP450: sertralina, nortriptilina y rifampicina.
2014
En este trabajo se han estudiado las interacciones farmacocinéticas del efavirenz (EFV) con tres fármacos metabolizados por el citocromo P450 (sertralina (SRT), nortriptilina (NT) y rifampicina (RFP)), utilizando la rata como animal de experimentación. El EFV se administró por vía intraduodenal (dosis = 10 mg) y los otros fármacos se administraron por vía intraduodenal (SRT y NT) o por vía oral (RFP). La coadministración de EFV y SRT (dosis de 5 mg y 10 mg) dio lugar a niveles plasmáticos de EFV mayores que los obtenidos en el grupo de control (animales administrados solo con EFV). Cuando se administró la dosis de 10 mg de SRT, se obtuvo un incremento estadísticamente significativo en los v…
Metabolism and Bioactivation of Corynoline With Characterization of the Glutathione/Cysteine Conjugate and Evaluation of Its Hepatotoxicity in Mice
2018
Corynoline (CRL), an isoquinoline alkaloid, is the major constituent derived from Corydalis bungeana Herba, which is a well-known Chinese herbal medicine widely used in many prescriptions. The purpose of this study was to comprehensively investigate the metabolism and bioactivation of CRL, and identify the CYP450 isoforms involved in reactive ortho-benzoquinone metabolites formation and evaluate its hepatotoxicity in mice. Here, high resolution and triple quadrupole mass spectrometry were used for studying the metabolism of CRL. Three metabolites (M1-M3) and four glutathione conjugates (M4-M7) of CRL ortho-benzoquinone reactive metabolite were found in vitro using rat and human liver micros…
The immunological implications of the new Vitamin D metabolism
2018
Vitamin D is actually a neurohormone whose pleiotropic activities encompass regulation of calcium-phosphate metabolism, cell proliferation and immunomodulation. Starting from a cutaneous compound, 2 hydroxylation steps are required to produce the active form of vitamin D3, named calcitriol [1, 25-(OH)2-cholecalciferol]. The second hydroxylation step may occur at different tis- sues and cell types, including kidney, lung, prostate, brain, immune cells and placenta. Based on the advancing knowledge of Cytochrome P450 functions, a new conception of Vitamin D metabolism emerged. It implies that, depending on the site where the second hydroxylation step occurs, the active hormone can act as a ca…
Recent advances in computational design of potent aromatase inhibitors: open-eye on endocrine-resistant breast cancers.
2019
Introduction: The vast majority of breast cancers (BC) are estrogen receptor positive (ER+). The most effective treatments to fight this BC type rely on estrogen deprivation therapy, by inhibiting the aromatase enzyme, which performs estrogen biosynthesis, or on blocking the estrogens signaling path via modulating/degrading the estrogen's specific nuclear receptor (estrogen receptor-?, ER?). While being effective at early disease stage, patients treated with aromatase inhibitors (AIs) may acquire resistance and often relapse after prolonged therapies. Areas covered: In this compendium, after an overview of the historical development of the AIs currently in clinical use, and of the computati…
Frontiers of metal-coordinating drug design
2020
INTRODUCTION: The occurrence of metal ions in biomolecules is required to exert vital cellular functions. Metal-containing biomolecules can be modulated by small-molecule inhibitors targeting their metal-moiety. As well, the discovery of cisplatin ushered the rational discovery of metal-containing-drugs. The use of both drug types exploiting metal–ligand interactions is well established to treat distinct pathologies. Therefore, characterizing and leveraging metal-coordinating drugs is a pivotal, yet challenging, part of medicinal chemistry. AREA COVERED: Atomic-level simulations are increasingly employed to overcome the challenges met by traditional drug-discovery approaches and to compleme…