2 edition of Parallel organs in drug and metabolism processing: the liver and kidney found in the catalog.
Parallel organs in drug and metabolism processing: the liver and kidney
InГ©s Anna Maria de Lannoy
Written in English
Advisor: Pang, K.S.
|The Physical Object|
|Number of Pages||224|
A microfluidic approach for in vitro assessment of interorgan interactions in drug metabolism using intestinal and liver slices. Lab C . CiteScore: ℹ CiteScore: CiteScore measures the average citations received per peer-reviewed document published in this title. CiteScore values are based on citation counts in a range of four years (e.g. ) to peer-reviewed documents (articles, reviews, conference papers, data papers and book chapters) published in the same four calendar years, divided by the number of.
This might yield significant benefits in drug testing, where the full effects of a compound are often not clear until processing in the liver or excretion from the kidney is accounted for. For the majority of drugs, metabolism is the major pathway of elimination [12, 13]. The primary organ involved is the liver, although the gastrointestinal (GI) tract, kidney, lung and skin may also contain drug metabolising enzymes and may contribute to regional concentrations of the drug .
With most psychoactive substances, first pass liver metabolism can make a very significant difference in the amount of the drug that ends up reaching the brain and other organs. Clinically, first-pass metabolism is important when the fraction of the dose administered that escapes metabolism is small and variable. The liver is usually assumed to be the major site of first-pass metabolism of a drug administered orally, but other potential sites are the gastrointestinal tract, blood, vascular endothelium, lungs, and the.
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The primary objective of drug metabolism is to facilitate a drug’s excretion by increasing its water solubility (hydrophilicity). The involved chemical modifications incidentally decrease or increase a drug’s pharmacological activity and/or half-life, the most extreme example being the metabolic activation of inactive prodrugs into active drugs, e.g.
of codeine into morphine by CYP2D6. The liver plays a central role in metabolism of nutrients, synthesis of glucose and lipids, and detoxification of drugs and xenobiotics. The major pathways in the liver are glucose, fatty acids Author: John Y L Chiang.
Since the liver is the principal organ related to drug metabolism, it is extremely important to accurately predict its metabolic ability and toxicity during the drug discovery process.
However, hepatocytes used for in vitro screening lose many of their original functions and by: Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems.
More generally, xenobiotic metabolism (from the Greek xenos "stranger" and biotic "related to living beings") is the set of metabolic pathways that modify the chemical structure of xenobiotics, which are compounds foreign to an organism's normal biochemistry, such as any drug.
The first experiment was designed to test drug effects on 2 different networks of 3 organ chips (gut- liver-kidney in one, and liver-kidney-bone marrow in the second) linked by a fluidic network.
The central compartment includes the well-perfused organs and tissues (heart, blood, liver, brain and kidney) with which drug equilibrates rapidly. Peripheral Compartment(s) The peripheral compartment(s) include(s) those organs (e.g., adipose and skeletal muscle) which are less well-perfused, and with which drug therefore equilibrates more.
Background Pharmacokinetics. The following is a short review of basic pharmacokinetic principles focusing on hepatic clearance.Drug absorption, nonrenal clearance, and volume of distribution of drugs are in fact altered by CRF via changes in hepatic clearance, intestinal absorption and first pass metabolism, hepatic, renal, and intestinal transport, plasma protein binding, and tissue binding.
The liver weighs approx. kg ( lb). It is both the largest internal organ and the largest gland in the human body. It is located in the upper abdomen, with 3 quarters in the right and 1 quarter in the left upper quadrant of the abdominal cavity.
The liver is the second largest organ in the body after the skin; it performs several processes that are extremely important to maintain homeostasis, and it is highly irrigated, receiving approximately 25% of the cardiac output. Therefore, the liver is the major organ responsible for the metabolism of various endogenous and exogenous compounds.
Organ-on-a-chip. Organ-on-a-chip is a microfluidic cell culture device that is a more physiologically relevant in vitro model than cells cultured in dishes. Important features include continuously perfused chambers inhabited by living cells arranged to simulate tissue- and organ-level physiology (Fig.
2).So far, several individual organ-on-chips have been developed, including gut-on-a. With a second multi-organ chip configuration comprising fluidically-linked liver, kidney and bone marrow chips, the team also investigated the pharmacological effects of cisplatin, a chemotherapeutic drug commonly used in cancer treatments, which is usually administered intravenously and displays unwanted toxicity in the kidney and bone marrow.
The drug metabolism study was carried out using liver and kidney S9 fractions of rats (male), dogs (male), and humans (mix of male and female). In N -acetylation metabolism studies of SAC and SACS, the reaction mixtures ( μ l) containing M phosphate buffer (pH), 5 μ M SAC or SACS, 2 mM acetyl-CoA, and each S9 fraction (– mg.
The second study, “Quantitative prediction of human pharmacokinetic responses to drugs via fluidically coupled vascularized organ chips,” saw the scientists put the Interrogator to use and apply a new computational model they developed to two different sets of three organ chips – Gut, Liver and Kidney, and Liver, Kidney, and Bone Marrow.
Given the broad distribution of peptidases in the body, several tissues, such as the liver, kidney, lung, blood, nasal epithelial cells, placenta and skin, have the capacity to metabolize peptides.
We compared the metabolic characteristics of peptides in these tissues and. Liver organoid biobanks can also be established from healthy liver cells and used as a platform for predicting drug-induced liver injury (DILI), the main reason for acute liver failure and the primary cause of drug removal from the market While human primary hepatocytes are currently the ‘gold-standard’ for drug metabolism and toxicity.
Because the organ chips contain an endothelium-lined vascular channel, Ingber proposed in that it might be possible to create a human “body-on-chips” by transferring fluids between the vascular channels of many different types of organ chips to mimic blood flow, and assessing drug PK/PD behaviors across the entire linked system.
Inspired by this vision and the realization that. Drug development is an extremely arduous and costly process, and failure rates in clinical trials that test new drugs for their safety and efficacy in.
Metabolic disease - Metabolic disease - Disorders of lipid metabolism: Lipids are large, water-insoluble molecules that have a variety of biological functions, including storing energy and serving as components of cellular membranes and lipoproteins.
Cells that line the small intestine absorb dietary lipids and process them into lipoprotein particles that enter the circulation via the. With a second multi-Organ Chip configuration comprising fluidically-linked Liver, Kidney, and Bone Marrow Chips, the team investigated the pharmacological effects of cisplatin, a chemotherapeutic drug commonly used in cancer treatments, which is administered intravenously and displays unwanted toxicity in the kidney and bone marrow.
Organ-on-a-chip academic research is in its blossom. Drug toxicity evaluation is a promising area in which organ-on-a-chip technology can apply. A unique advantage of organ-on-a-chip is the ability to integrate drug metabolism and drug toxic processes in a single device, which facilitates evaluation of toxicity of drug metabolites.
Human organ-on-a-chip has been fabricated and used to assess. These products are results of metabolism, and they leave a human body in the form of sweat, urine and faeces.
Even though several organs are associated with this process, the term excretory system is used for organs directly related to the expel procedure.
It includes the kidneys, sweat glands, liver .Metabolism The drug is “changed” so it can be Usually occurs in liver and kidney (other organs sometimes involved) Metabolism Most oxidative metabolism occurs via CYP system.
Image from: Guzman, Cambridge MedChem Consulting. Bile 3. Hepatic extraction and clearance. The liver is an extremely complex organ, tasked with so many of the vital functions that maintain and sustain health and life.
Liver disease in the horse can develop as .