Toxicokinetics
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Toxicokinetics
Toxicokinetics (often abbreviated as 'TK') is the description of both what rate a chemical will enter the body and what occurs to excrete and metabolize the compound once it is in the body. Relation to Pharmacokinetics It is an application of pharmacokinetics to determine the relationship between the systemic exposure of a compound and its toxicity. It is used primarily for establishing relationships between exposures in toxicology experiments in animals and the corresponding exposures in humans. However, it can also be used in environmental risk assessments in order to determine the potential effects of releasing chemicals into the environment. In order to quantify toxic effects, toxicokinetics can be combined with toxicodynamics. Such toxicokinetic-toxicodynamic (TKTD) models are used in ecotoxicology (seecotoxmodelsa website on mathematical models in ecotoxicology). Similarly, physiological toxicokinetic models are physiological pharmacokinetic models developed to describe an ...
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Pharmacokinetics
Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to determining the fate of substances administered to a living organism. The substances of interest include any chemical xenobiotic such as: pharmaceutical drugs, pesticides, food additives, cosmetics, etc. It attempts to analyze chemical metabolism and to discover the fate of a chemical from the moment that it is administered up to the point at which it is completely eliminated from the body. Pharmacokinetics is the study of how an organism affects a drug, whereas pharmacodynamics (PD) is the study of how the drug affects the organism. Both together influence dosing, benefit, and adverse effects, as seen in PK/PD models. Overview Pharmacokinetics describes how the body affects a specific xenobiotic/chemical after administration through the mechanisms of absorption and distribution, as ...
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Pharmacokinetics
Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to determining the fate of substances administered to a living organism. The substances of interest include any chemical xenobiotic such as: pharmaceutical drugs, pesticides, food additives, cosmetics, etc. It attempts to analyze chemical metabolism and to discover the fate of a chemical from the moment that it is administered up to the point at which it is completely eliminated from the body. Pharmacokinetics is the study of how an organism affects a drug, whereas pharmacodynamics (PD) is the study of how the drug affects the organism. Both together influence dosing, benefit, and adverse effects, as seen in PK/PD models. Overview Pharmacokinetics describes how the body affects a specific xenobiotic/chemical after administration through the mechanisms of absorption and distribution, as ...
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Toxin
A toxin is a naturally occurring organic poison produced by metabolic activities of living cells or organisms. Toxins occur especially as a protein or conjugated protein. The term toxin was first used by organic chemist Ludwig Brieger (1849–1919) and is derived from the word toxic. Toxins can be small molecules, peptides, or proteins that are capable of causing disease on contact with or absorption by body tissues interacting with biological macromolecules such as enzymes or cellular receptors. Toxins vary greatly in their toxicity, ranging from usually minor (such as a bee sting) to potentially fatal even at extremely low doses (such as botulinum toxin). Toxins are largely secondary metabolites, which are organic compounds that are not directly involved in an organism's growth, development, or reproduction, instead often aiding it in matters of defense. Terminology Toxins are often distinguished from other chemical agents strictly based on their biological origin. Le ...
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Toxicology
Toxicology is a scientific discipline, overlapping with biology, chemistry, pharmacology, and medicine, that involves the study of the adverse effects of chemical substances on living organisms and the practice of diagnosing and treating exposures to toxins and toxicants. The relationship between dose and its effects on the exposed organism is of high significance in toxicology. Factors that influence chemical toxicity include the dosage, duration of exposure (whether it is acute or chronic), route of exposure, species, age, sex, and environment. Toxicologists are experts on poisons and poisoning. There is a movement for evidence-based toxicology as part of the larger movement towards evidence-based practices. Toxicology is currently contributing to the field of cancer research, since some toxins can be used as drugs for killing tumor cells. One prime example of this is ribosome-inactivating proteins, tested in the treatment of leukemia. The word ''toxicology'' () is a neocla ...
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Ecotoxicology
Ecotoxicology is the study of the effects of toxic chemicals on biological organisms, especially at the population, community, ecosystem, and biosphere levels. Ecotoxicology is a multidisciplinary field, which integrates toxicology and ecology. The ultimate goal of ecotoxicology is to reveal and predict the effects of pollution within the context of all other environmental factors. Based on this knowledge the most efficient and effective action to prevent or remediate any detrimental effect can be identified. In those ecosystems that are already affected by pollution, ecotoxicological studies can inform the choice of action to restore ecosystem services, structures, and functions efficiently and effectively. Ecotoxicology differs from environmental toxicology in that it integrates the effects of stressors across all levels of biological organisation from the molecular to whole communities and ecosystems, whereas environmental toxicology includes toxicity to humans and often focus ...
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PBPK
Physiologically based pharmacokinetic (PBPK) modeling is a mathematical modeling technique for predicting the absorption, distribution, metabolism and excretion (ADME) of synthetic or natural chemical substances in humans and other animal species. PBPK modeling is used in pharmaceutical research and drug development, and in health risk assessment for cosmetics or general chemicals. PBPK models strive to be mechanistic by mathematically transcribing anatomical, physiological, physical, and chemical descriptions of the phenomena involved in the complex ADME processes. A large degree of residual simplification and empiricism is still present in those models, but they have an extended domain of applicability compared to that of classical, empirical function based, pharmacokinetic models. PBPK models may have purely predictive uses, but other uses, such as statistical inference, have been made possible by the development of Bayesian statistical tools able to deal with complex models. T ...
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Absorption (pharmacokinetics)
Absorption is the journey of a drug travelling from the site of administration to the site of action. The drug travels by some route of administration (oral, topical-dermal, etc.) in a chosen dosage form (e.g., tablets, capsules, or in solution). Absorption by some other routes, such as intravenous therapy, intramuscular injection, enteral nutrition, is even more straightforward and there is less variability in absorption and bioavailability is often near 100%. Intravascular administration does not involve absorption, and there is no loss of drug. The fastest route of absorption is inhalation. Absorption is a primary focus in drug development and medicinal chemistry, since a drug must be absorbed before any medicinal effects can take place. Moreover, the drug's pharmacokinetic profile can be easily and significantly changed by adjusting factors that affect absorption. Dissolution In the most common situation, a tablet is ingested and passes through the esophagus to the st ...
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Metabolite
In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, catalytic activity of their own (usually as a cofactor to an enzyme), defense, and interactions with other organisms (e.g. pigments, odorants, and pheromones). A primary metabolite is directly involved in normal "growth", development, and reproduction. Ethylene exemplifies a primary metabolite produced large-scale by industrial microbiology. A secondary metabolite is not directly involved in those processes, but usually has an important ecological function. Examples include antibiotics and pigments such as resins and terpenes etc. Some antibiotics use primary metabolites as precursors, such as actinomycin, which is created from the primary metabolite tryptophan. Some sugars are metabolites, such as fructose or glucose, which are both p ...
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Biotransformation
Biotransformation is the biochemical modification of one chemical compound or a mixture of chemical compounds. Biotransformations can be conducted with whole cells, their lysates, or purified enzymes. Increasingly, biotransformations are effected with purified enzymes. Major industries and life-saving technologies depend on biotransformations. Advantages and disadvantages Compared to the conventional production of chemicals, biotransformations are often attractive because their selectivities can be high, limiting the coproduction of undesirable coproducts. Generally operating under mild temperatures and pressures in aqueous solutions, many biotransformations are "green". The catalysts, i.e. the enzymes, are amenable to improvement by genetic manipulation. Biotechnology usually is restrained by substrate scope. Petrochemicals for example are often not amenable to biotransformations, especially on the scale required for some applications, e.g. fuels. Biotransformations can be s ...
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Acute Toxicity
Acute toxicity describes the adverse effects of a substance that result either from a single exposure or from multiple exposures in a short period of time (usually less than 24 hours). To be described as ''acute'' toxicity, the adverse effects should occur within 14 days of the administration of the substance. Acute toxicity is distinguished from chronic toxicity, which describes the adverse health effects from repeated exposures, often at lower levels, to a substance over a longer time period (months or years). It is widely considered unethical to use humans as test subjects for acute (or chronic) toxicity research. However, some information can be gained from investigating accidental human exposures (e.g., factory accidents). Otherwise, most acute toxicity data comes from animal testing or, more recently, ''in vitro'' testing methods and inference from data on similar substances. Measures of acute toxicity Regulatory values Limits for short-term exposure, such as ...
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Half-life
Half-life (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable atoms survive. The term is also used more generally to characterize any type of exponential (or, rarely, non-exponential) decay. For example, the medical sciences refer to the biological half-life of drugs and other chemicals in the human body. The converse of half-life (in exponential growth) is doubling time. The original term, ''half-life period'', dating to Ernest Rutherford's discovery of the principle in 1907, was shortened to ''half-life'' in the early 1950s. Rutherford applied the principle of a radioactive element's half-life in studies of age determination of rocks by measuring the decay period of radium to lead-206. Half-life is constant over the lifetime of an exponentially decaying quantity, and it is a characteristic unit for ...
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Medicinal Chemistry
Medicinal or pharmaceutical chemistry is a scientific discipline at the intersection of chemistry and pharmacy involved with designing and developing pharmaceutical drugs. Medicinal chemistry involves the identification, synthesis and development of new chemical entities suitable for therapeutic use. It also includes the study of existing drugs, their biological properties, and their quantitative structure-activity relationships (QSAR). Medicinal chemistry is a highly interdisciplinary science combining organic chemistry with biochemistry, computational chemistry, pharmacology, molecular biology, statistics, and physical chemistry. Compounds used as medicines are most often organic compounds, which are often divided into the broad classes of small organic molecules (e.g., atorvastatin, fluticasone, clopidogrel) and "biologics" (infliximab, erythropoietin, insulin glargine), the latter of which are most often medicinal preparations of proteins (natural and recombinant ant ...
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