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Clinical Pharmacology of Parenteral Dosage Forms
Published in Sandeep Nema, John D. Ludwig, Parenteral Medications, 2019
Most drugs begin to be metabolized after they enter the body. The majority of small-molecule drug metabolism is carried out in the liver by redox enzymes, termed cytochrome (CYP) P450 enzymes (ubiquitously expressed in the body). As metabolism occurs, a (parent) drug is chemically converted to metabolites. Metabolism eliminates the administered dose of a parent drug. When metabolites are pharmacologically inert, metabolism reduces pharmacological effects in the body as a parent drug is eliminated. Metabolites may also be pharmacologically active, sometimes more so than a parent drug (active metabolites).
Assessment of Human Exposure to Chemicals Through Biological Monitoring
Published in Frederick C. Kopfler, Gunther F. Craun, Environmental Epidemiology, 2019
Alfred M. Bernard, Robert R. Lauwerys
For chemicals which must be activated before reaching the target sites, the determination of the active metabolite or of a metabolite deriving from the activated form may be more relevant for the health risk assessment than that of the parent compound or of any other metabolite not involved in the toxic process. For example, the analysis of hexanedione, the metabolite responsible for the neurotoxicity of n-hexane, might be more useful than that of n-hexanol in urine or n-hexane in expired air for monitoring the exposure to this solvent [2].
Endophytic Streptomyces isolated from Ocimum tenuiflorum and Catharanthus roseus and its efficacy test to develop antibacterial fabric for wound caring
Published in The Journal of The Textile Institute, 2023
Reshma Ayswaria, Jancy Alfred, Gisha Gopalan, Rijesh Krishna
Extracellular metabolites present in the cell-free supernatant were separated by liquid-liquid extraction. Different solvents were used for the extraction of the crude active metabolite from the supernatant and then bioactivity of the organic layer was checked to confirm the presence of active crude metabolite in the presence of different solvents as a negative control. Activity was checked against MTCC culture and hospital samples to confirm wide spectrum activity and it is retained even after extraction. Among different solvents, chloroform extract showed better inhibition against test pathogens while comparing with the rest of the solvents. Zone of inhibition against P. aeruginosa, K. pneumoniae, MRSA and MTCC culture observed there is no inhibition in solvents which kept as negative control and there is no inhibition against E. coli by any extract, as given in Table 3. This method used for the separation of solute from one solvent to another, the two solvents being immiscible or partially miscible. Especially while doing water extract non polar solvents are the choice (Janardhan et al., 2014). The organic layer in which metabolite present was taken for bioactivity assay and comparing between these three extracts better efficacy observed for OT and CR, in the succeeding experiments these two extracts were used.
Occupational exposure to aflatoxins and health outcomes: a review
Published in Journal of Environmental Science and Health, Part C, 2019
Ruth Nabwire Wangia, Lili Tang, Jia-Sheng Wang
The epoxide is highly unstable, has a high affinity for DNA binding and easily reacts with the N7 atom of guanine to form pro-mutagenic DNA-adduct. DNA adducts resistant to DNA repair processes result in mutations, which ultimately leads to tumor formations.48,57 Alternatively, the epoxide can bind to plasma proteins such as albumin to form AF lysine albumin adducts.14,21,42 Quantification of adducts provides a measure of the amount of active metabolite in an organism.72 The presence of DNA adducts, albumin adducts, and AF metabolites in urine and blood when quantified can be used to assess AF exposure, internal dose, and biologically effective dose. Toxicity associated with the presence of AFB1-lysine adducts include nutritional interference and immune suppression in both animals and humans.73 The metabolic pathways of AFB1 are summarized in Figure 2 which was adapted from Bbosa 2003 with modifications.48
Application of the adverse outcome pathway (AOP) approach to inform mode of action (MOA): A case study with inorganic arsenic
Published in Journal of Toxicology and Environmental Health, Part A, 2018
Harvey J. Clewell, Janice W. Yager, Tracy B. Greene, P. Robinan Gentry
In applying the proposed AOP in an MOA framework, important chemical-specific characteristics that are critical to the interaction with the MIE needs to be considered. In particular, metabolism as well as other key aspects of the pharmacokinetics of the chemical of interest are essential factors in the development of the MOA. In the case of iAs, metabolism is critical to the interaction because not all arsenic (As) compounds possess the necessary structure to interact with proteins that initiate the cellular response. Application of an AOP in the development of an MOA also requires the explicit consideration of dose-response. Dose-response is not an explicit part of an AOP, which consists only of response–response relationships. This is focused on understanding the precision with which the state of the downstream KE can be predicted by the knowledge of the state of the upstream KE (OECD 2018). These relationships may be expressed in ways other than dose–response relationships (e.g., correlations, simple mathematical equations, dose-dependent transitions, points of departure). The tacit assumption in using an AOP is that a sufficient concentration of the chemical or its active metabolite is present to interact with a particular cellular component. At a lower or higher concentration, the MOA may change, as will be discussed in the case of iAs.