8,991 research outputs found
Network pharmacology and epilepsy
No full textIn contrast with the reductionist “one gene, one target, one drug” approach, network pharmacology proposes the use of multi-target therapies, a strategy that seems particularly suitable to treat disorders of complex etiology, among them epilepsy. As a matter of fact, most of the existing antiepileptic drugs are indeed multi-target unintended agents. Whereas a number of authors have recently advocated the use of network-based approximations in the antiepileptic drug discovery fi eld, such strategy has so far not produced deliverables. Here, we review some practical considerations which could be used to assist in silico and wet screening for novel antiepileptic agents.Fil: Talevi, Alan. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Cátedra de Química Medicinal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentin
Biorelevant dissolution media
No full textBiorelevant dissolution media are aqueous solutions or suspensions whose composition and physicochemical characteristics closely resemble human fluids found along the different portions of the gastrointestinal tract, developed to study the solubility and/or dissolution profile of orally administered drugs in a more physiologically relevant manner.Fil: Ruiz, María Esperanza. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; ArgentinaFil: Talevi, Alan. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentin
Free Drug Theory
No full textThe free drug theory (sometimes also termed free drug hypothesis) provides a conceptual framework increasingly used to understand pharmacokinetics/pharmacodynamics (PK/PD) relationships [1]. It underlines the central role of free (or unbound) drug concentration at the site of action (the surroundings of the drug target) as determinant of in vivo efficacy and pharmacokinetics. A deep understanding of this theory can also be helpful to establish in vitro-in vivo correlations or, alternatively, to provide explanations to absence of clear correlations between in vitro and in vivo studies.Fil: Talevi, Alan. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Bellera, Carolina Leticia. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentin
Biliary Drug Excretion
No full textBiliary excretion refers to the elimination of endogenous and exogenous compounds (and their metabolites) predominantly by secretion through the canalicular membrane into the canaliculus, a space formed between the apical membranes of neighboring hepatocytes. The excretion process is completed when the bile transports its contents to the gut and they are ultimately eliminated in feces (some compounds secreted into the bile, however, may be subject to reabsorption from the intestine, entering into enterohepatic cycling).Fil: Talevi, Alan. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Bellera, Carolina Leticia. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentin
The importance of drug repurposing in the field of antiepileptic drug development
No full textDrug repurposing involves finding new therapeutic uses for existing drugs, including marketed, discontinued, shelved, and investigational drugs. The advantages of this strategy are many: reduced drug development timeline, best chances of surviving Phase II and Phase III clinical trials, simplified dosage form development, and, of course, added value to drugs belonging to a company or laboratory portfolio. The relatively high number of antiepileptic drugs which have been successfully repurposed and the fact that many drugs from other categories have proven anticonvulsant effects at the preclinical and even clinical level suggest that this strategy should be widely exploited in the antiepileptic drug discovery field. Here, we present an overview of the current approaches to drug repurposing, along with practical considerations to face a drug repurposing campaign to find new treatments for epilepsy and novel therapeutic uses for antiepileptic drugs.Fil: Talevi, Alan. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Cátedra de Química Medicinal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentin
Drug Binding to Plasma Proteins
No full textAfter absorption, most drugs will distribute heterogeneouslyacross tissues and organs, with the total drug concentration in plasmagenerally not being representative of the total concentration in other tissues.The main factors that explain the non-homogeneous distribution are the affinityof the drug for drug transporters and/or for tissue constituents. In plasma,drug molecules can reversibly interact with plasma proteins (mainly albumin, α1-acidglycoprotein (AAG), and, to a lesser extent, lipoproteins). Due to its size,the complex between the drug and a plasma protein cannot readily leave theintravascular space through transcellular diffusion across the endothelia. Thefree drug theory assumes that only the unbound drug fraction freely permeatesthrough biological barriers, directly contributing to drug distribution: ifcertain assumptions are met (e.g., absence of active transport), only unbounddrug concentrations will be equal at steady state.Fil: Talevi, Alan. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; ArgentinaFil: Bellera, Carolina Leticia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentin
Transcytosis in Drug Absorption and Distribution
No full textThe term transcytosis designates the vesicular transcellular transport of molecules from one side of a polarized epithelial or endothelial cell to the other. It is a key process for the absorption and/or distribution of large molecules, e.g., macromolecules, or, in some cases, more complex entities, e.g., nanoscale particles/constructs.Epithelial cell layers line the outer surfaces of organs throughout the body, as well as the inner surfaces of cavities in many internal organs. They act as selective barriers, regulating the transference of molecules (and, at times, supramolecular structures) in and out of organs. Endothelial cell layers, which line the interior surface of the blood vessels, accomplish an equivalent function in separating the vascular space from the extravascular tissues. They are thus critical barriers in the processes of drug absorption and distribution for systemic...Fil: Talevi, Alan. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Bellera, Carolina Leticia. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentin
Personalized Medicine and Drug Metabolism
No full textThe Precision Medicine Initiative (a nationwide programsponsored by the United States National Institutes of Health) defines precisionmedicine as an emerging approach for disease treatment and prevention thattakes into account individual variability in genes, environment, and lifestylefor each person. Precision medicine is closely related to personalized andstratified medicine, and all these terms are frequently appliedinterchangeably, although subtle distinctions between them have been underlined.At present, it is clear that more efficacious and safer therapeuticinterventions are to be expected if tailored to the specific variations in aperson?s genome, transcriptome, proteome, and metabolome. The scope ofpersonalized medicine has been considerably expanded by genotyping technologies(particularly, next-generation sequencing and microarray biochips), as well asstate-of-the-art computing able to process large datasets.Fil: Talevi, Alan. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Bellera, Carolina Leticia. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentin
Enterohepatic Recycling
No full textBroadly speaking, enterohepatic recycling (or enterohepaticcirculation) involves the circulation of metabolized and non-metabolizedcompounds (including physiologic compounds and xenobiotics) between theintestine and the liver. Some xenobiotics and some endogenous substances (e.g.,bile acids) can be reabsorbed after their elimination into the intestineby the liver, entering an enterohepatic cycle. Enterohepatic circulation can beregarded as the phenomenon of the transport of chemical compounds from theliver to the bile, which eventually drains into intestine and is followed byreabsorption and then back into the liver. The intestinal microbiota plays acentral role in the enterohepatic recycling phenomenon. Enterohepaticcirculation increases the elimination half-life of many drugs (thus prolongingtheir action) and causes multiple peaks in the plasma drug concentration-timeprofile, which are frequently elusive in terms of pharmacokinetic modeling. Insome cases, enterohepatic recycling may have a substantial toxicological impact,as it can retoxify already detoxified xenobiotic molecules and some organs,i.e., the intestine and the liver, may be reiteratively exposed to the drug.Fil: Talevi, Alan. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; ArgentinaFil: Bellera, Carolina Leticia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentin
Enzyme Induction and Drug Metabolism
No full textEnzyme induction is one of the most important underlying mechanism of drug-drug interactions (DDIs). It can be defined as an increase in the biosynthesis of metabolizing enzymes after the exposure of the organism to environmental factors (e.g., chemical agents such as drugs or pollutants) or due to physiological/pathophysiological conditions (e.g., hormone or cytokine release). It is mediated by increased transcription of mRNA encoding the genes for drug-metabolizing enzymes; the augmented enzyme levels lead to the increase of the maximum reaction velocity Vmax, which in turn results in a diminished exposure to the parent drug and an increased exposure to the drug metabolite(s) produced by the induced enzyme (or by subsequent metabolizing steps in the same metabolic pathway). The result can be either a decrease or an increase in the pharmacological effect of the drug, depending upon whether the parent drug or its metabolite is the active entity, respectively.Fil: Talevi, Alan. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; ArgentinaFil: Bellera, Carolina Leticia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentin
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