Drug metabolites

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  • In a certain sense, the field of drug metabolism (DM) is standing still. More specifically, the basic experiment of drug metabolism (i.e., administering a new drug to an animal or human and determining the structures, amounts, and disposition of the metabolites) has changed very little over a period of decades. Remarkably, the experimental design and resulting data set from a typical absorption, distribution, metabolism, and excretion (ADME) study conducted today would be instantly recognized and understood by DM scientists from 50 years ago.

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  • Foreword: It was with great pleasure that I accepted the invitation to write the foreword for Drugs and Poisons in Humans. A Handbook of Practical Analysis. Dr. Osamu Suzuki and Dr. Mikio Yashiki, two outstanding Japanese scientists, fi rst published the Handbook in Japanese in 2002. Specialists throughout Japan contributed analytical methods for a wide variety of therapeutic and illicit drugs, pesticides, and natural toxins and alkaloids. In fact, rarely has such a wide spectrum of analytes and metabolites been addressed within a single reference manual....

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  • Introduction: Blood, urine and stomach contents (including gastric lavage fluid and vomitus) are usually used as specimens for analysis of drugs and poisons for living subjects. A blood concentration of a toxin can be an indicator for estimation of intoxication degree. Urine sometimes contains large amounts of metabolites and/or an unchanged form of a toxin; it contains low levels of proteins, which usually interfere with analysis, and thus is suitable for screening tests using immunoassays without tedious pretreatments.

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  • Introduction: Amphetamines are a group of drugs stimulating the central nervous system; they act on the cerebral cortex to enhance psychic activities, resulting in the removal of general fatigue and drowsiness and thus in the transient improvement of working efficiency. Their abuse causes dependence, hallucination, delusion and changes in personality. Because of such harmfulness of the drugs, their use and possession are prohibited by the Stimulant Drugs Control Law in Japan [1].

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  • Introduction: Methanol (methyl alcohol) poisoning accidents take place most frequently by drinking it in mistake for ethanol. Methanol poisoning is not due to the effect of methanol itself, but due to toxicity of its metabolites. Methanol is rapidly absorbed into human body through the airway mucous membranes, digestive tract mucous membranes or the skin; it is metabolized into formaldehyde (formalin, HCHO) and then formic acid (HCOOH) by the actions of alcohol dehydrogenase and aldehyde dehydrogenase, respectively.

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  • Introduction: Nicotine is a main water-soluble alkaloid being contained in the tobacco plant (Nicotiana tabacum), which acts as an inducing compound for smoking-dependence. Twelve kinds of nicotine metabolites are known in rats [1]. Among them, cotinine is the major metabolite of nicotine; the half-life (T1/2) of cotinine is much longer (10–20 h) than that of nicotine (24–84 min). The qualitative analysis of cotinine in urine and saliva is being thus carried out as indicators for smoking during its abstinence therapy and for confirming passive smoking.

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  • Natural products are a constant source of potentially active compounds for the treatment of various disorders. The Middle East and tropical regions are believed to have the richest supplies of natural products in the world. Plant derived secondary metabolites have been used by humans to treat acute infections, health disorders and chronic illness for tens of thousands of years. Only during the last 100 years have natural products been largely replaced by synthetic drugs.

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  • Introduction: Acetaminophen (paracetamol, APAP) ( Figure 3.1) has been being used as an excellent analgesic-antipyretic for a long time, and is included as an ingredient in many over-the-counter drugs of analgesics and cold drugs. However, when APAP is ingested in large amounts, it was reported to cause liver disorders [1]. For analysis of APAP, HPLC [2–18], LC/MS [19], LC/MS/MS [20], GC [21], GC/MS [22, 23] and capillary electrophoresis [24, 25] are being used. Among the methods, HPLC is most popular for its analysis.

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  • Delayed hypersensitivity mechanisms directed by drug-specific T cells are probably the most important mechanisms in the etiology of the most common drug eruptions—morbilliform exanthems—and also of rare and severe forms such as hypersensitivity syndrome, acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Drugspecific T cells have been detected in these types of drug eruptions. Contrary to what has been believed for years, the antigen is more often the native drug itself than its metabolites.

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  • Food safety is of great importance to consumers. To ensure the safety of the food supply and to facilitate international trade, government agencies and international bodies establish standards, guidelines, and regulations that food producers and trade partners need to meet, respect, and follow. A primary goal of national and international regulatory frameworks for the use of veterinary drugs, including antimicrobials, in food-producing animals is to ensure that authorized products are used in a manner that will not lead to non-compliance residues.

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  • Introduction: The plant Cannabis sativa L. has a long history for human being since about BC 2000 for its use as fiber material, food and folk medicine; cannabis (hemp, marijuana) means the whole plant itself and its dried products except for its stem and seeds. The word “hashish” is mainly used for the resin of the cannabis plant.

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  • Introduction: Hydrogen sulfide (H2S) is a colorless gas with the smell of putrid eggs; it can exist in both nonionic and ionic forms in aqueous solution. The ratio of the nonionic form to the total ionized one is influenced by concentration of hydrogen ion in the solution. Under acidic conditions, H2S does not ionized and evaporated from water; under alkaline conditions it is easily ionized and retained in the solution.

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  • Nowadays, Chromatography is the most versatile and widespread technique employed in modern chemical analysis and plays a vital role in the advancement of chemistry, biology, medicine and related fields of research. Because of the inherent simplicity and ease of operation, it can be used together with a wide range of detection systems, including electrochemical, photometric and mass spectrometry, being an invaluable laboratory tool for the separation and identification of compounds.

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  • Introduction: Cocaine is an alkaloid being contained in the leaves of Erythroxylon coca Lam. or Erythroxylon novogranatense (Morris) Hieronymus of Erythroxylaceae plants. The compound is being used as a local anaesthetic. It also shows stimulating action on the central nervous system; when it is used continuously, psychic dependence on its use appears, resulting in its chronic toxicosis [1]. Cocaine is being abused worldwide; its abuse is most serious in the north and south American continents. Fortunately, in Japan, its abuse is not so many; but it cannot be overlooked.

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  • Breast cancer is the most common form of incident cancer and the dominant cause of cancer-related death among women aged 0-74 across the European Union. Female mortality due to lung cancer is significantly lower than that of breast cancer, and is also lower in women than men, but has been steadily rising (Bosetti et al 2008, Boyle Lewin 2008). Across the EU/EEA countries, men are more affected by HIV than women, with an infection ratio of 2:1. In women the predominant routes of transmission are heterosexual contact and injection drug use (ECDC 2008a).

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  • The liver is the most important organ in which drugs are structurally altered. Some of the resulting metabolites may be biologically inactive, some active and some toxic (see Chapter 7).The liver is exposed to drugs in higher concentrations than are most organs because most are administered orally and are absorbed from the gastrointestinal tract.Thus the whole dose must pass through the liver to reach the systemic circulation.

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  • The financial statements of Koninklijke Philips Electronics N.V. (the ‘Parent Company') are included in the statements of the Philips Group. The unconsolidated statements of income of Koninklijke Philips Electronics N.V. therefore reflect only the net after-tax income from affiliated companies and other income after taxes. The accompanying notes are an integral part of the consolidated financial statements. Presentation balance sheet and income statement In 1997, the Company changed the format of its consolidated balance sheet presentation.

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  • The IRS also faces significant enforcement challenges posed by the complexity and magnitude of the international financial system. As technology continues to advance and cross-border transactions rise, the IRS faces the growing challenge created by economic globalization. Over the past few years, the IRS has taken action to coordinate international tax compliance issues.

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  • Assuming that (1) new information will correct or improve the firm's prior beliefs and (2) the firm has the technical and regulatory flexibility to alter its decisions, we are ultimately concerned with the economic value of the changed decision. Given that the firm will "re- optimize" based on the new, better information, what is the value of that re-optimization? Assume that Chemical A's cost was found to be grossly underestimated and that the firm was able to identify a substitute input B whose true cost was substantially lower.

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  • Analysis of differences in content of nutrients and other substances in livestock products (meat, dairy, eggs) was more limited given the smaller evidence base. Analysis was conducted on nutrients or nutrient groups for which numeric data were provided in at least 5 of the 25 livestock product studies identified by the review.

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