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Biotransformation of Xenobiotics in Living Systems—Metabolism of Drugs: Partnership of Liver and Gut Microflora
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2020
In humans, most drugs belong to xenobiotics, since people do not produce them naturally. Drug biotransformation refers to as the biochemical modification of pharmaceutical substances by living organisms, where specialized enzymatic systems play a crucial role in the conversion of one chemical species to another (Liu et al., 2017). The terms biotransformation and metabolism are commonly used as synonyms, especially when related to drugs. The term metabolism is often used to describe the total fate of a xenobiotic, which includes absorption, distribution, biotransformation and elimination. However, metabolism is commonly used to mean biotransformation, which is understandable taking into account that the products of xenobiotic biotransformation are known as metabolites (Parkinson et al., 2001).
Nomenclature and Terminology
Published in Jack Daugherty, Assessment of Chemical Exposures, 2020
Adverse effects from chronic exposures are observed when absorption of the contaminant in body tissues is greater than biotransformation and excretion combined. If the excretion rate is less than the rate of absorption (mass out < mass in) the contaminant accumulates in the body. Steady state occurs when absorption = excretion (mass in = mass out). Biotransformation is a specific phase of metabolism during which the contaminant (called a xenobiotic in the body) is transformed to another chemical by a biotic system, typically an enzyme. Besides biotransformatiom, metabolism processes include absorption, distribution, and excretion. A primary effect is one where the stressor acts on the ecological component of interest, or the human target organ, itself, not through effects on other components of the ecosystem. A direct effect is synonymous with primary effect. A secondary effect of a stressor acts on supporting components of a body or an ecosystem, which in turn affect the physiological or ecological component of interest. A synonymous term is indirect effect. Recovery is the rate and extent of return of an individual or a population or community to a condition that existed before the introduction of a stressor. Due to the dynamic nature of physiological and ecological systems, the attributes of a recovered person or system must be carefully defined. Though the exposure assessor is not typically involved in the recovery phase, he or she may be called upon to provide exposure data, modeling expertise, or other information.
Nonclinical Studies
Published in John M. Centanni, Michael J. Roy, Biotechnology Operations, 2016
John M. Centanni, Michael J. Roy
Biopharmaceuticals eventually change in the body to another form and become metabolically inactive through normal processes such as enzymatic degradation. A few biomolecules, such as the DNA in a genetic therapy or a pluripotent-cell-derived product, may not follow this rule, because they are developed for the purpose of longevity in the body. Yet, biotransformation, a term used to describe any biological process that converts the original product to another molecular format, is the rule that applies to biopharmaceuticals. In some cases, biotransformation enhances the therapeutic activity, whereas in others, it decreases, limits, or terminates the biological activity. Physiological, genetic, and environmental factors may be, and often are, involved in biotransformation. Although we can establish the average time of biological activity in a given population, it has been nearly impossible to reliably predict, for a single individual or animal, how long a particular biopharmaceutical will remain active. Living organisms are quite diverse, when it comes to processing biopharmaceuticals. Further complicating the picture, the coadministration of two compounds can have unexpected effects, because metabolic drug interactions are possible. Drug interactions can impact absorption, distribution, pharmacokinetics, metabolism, or excretion, and many patients take two or more drugs or biopharmaceuticals. Metabolism and biotransformation studies can assist in understanding the overall pharmacological profile of any product.
MOLECULAR DOCKING INVESTIGATION AND PHARMACOKINETIC PROPERTIES PREDICTION OF SOME ANILINOPYRIMIDINES ANALOGUES AS EGFR T790M TYROSINE KINASE INHIBITORS
Published in Egyptian Journal of Basic and Applied Sciences, 2021
Muhammad Tukur Ibrahim, Adamu Uzairu, Gideon Adamu Shallangwa, Sani Uba
All the reported compounds have absorbance value between 76.641 and 94.419% as the values passed the minimum recommended values of 30% which indicates good human intestinal absorption. The minimum recommended values for the blood–brain barrier (BBB) and central nervous system permeability is > 0.3 to < −1 Log BB and > −2 to < −3 Log PS, respectively. As for these compounds, Log BB is > −1 for all which implies that the compounds are better distributed to brain and Log PS for all is > −2, which are considered to penetrate the central nervous system. The enzymatic metabolism of drugs shows the biotransformation of a drug in the body. It is, therefore, very important to put into consideration the metabolism of drugs, as such the cytochrome P450 plays an important role in drug metabolism. CYP families involved in drug metabolism were 1A2, 2C9, 2C19, 2D6, and 3A4, respectively. The most important among the mention CYP families is 3A4 which all the reported compounds were found to be substrate and inhibitors of it. Total clearance is an indicator, which describes the relationship between the rate of elimination of the drug and its concentration in the body. The reported compounds showed high value of total clearance but within the accepted limit of a drug molecule in the body. Furthermore, all the reported compounds were found to be nontoxic. The overall ADMET properties of these compounds indicate their good pharmacokinetic profiles (Table 2).
Understanding the fundamentals of microbial remediation with emphasize on metabolomics
Published in Preparative Biochemistry & Biotechnology, 2022
Vaishnavi Jeevanandam, Jabez Osborne
The genetic pathway gets altered when the microorganism is in contact with the xenobiotic compounds. Microbes undergo the process called biotransformation in which the toxic xenobiotic compounds are transformed into one form to another. In this process microbes generate wide range of metabolites based on the xenobiotic compounds. These metabolites are produced with more specificity. The biotransformation process includes oxidation, reduction, isomerization, hydrolysis, addition of new carbon bonds, new functional groups and condensation.[56] The enzymatic mechanism effectively involves the degradation of azo dye molecules by oxidoreductase enzymes. These enzymes are involved in the decolourization and reduction of toxic compounds into less toxic form.57 In the study of Sinha and Osborne,[24] the enzymes such as DCIP reductase, laccase, lignin peroxidases have significantly been observed in higher decolourization by the fungal strain Aspergillus niger. The laccase enzyme breaks down the azo bond N=N which produce pyrolo (1,2-A) pyrazine-1,4-Dione and 2- propanoic acid. The propanoic acid is the major intermediate of Aspergillus niger which gets converted into succinyl co-A in the presence of gluctalconate Co-A transferase further converted to give benzoic acid. According to Dash and Osborne[23] the degradation of pesticides such as profenofos and quinalphos. The initial breakdown of pesticides by hydrolysis whereas, organophosphate hydrolase (OPH) enzymes is effective in P-O bonds when compared to P-S bonds. The end product produced by Kasakonia sp by the enzymatic breakdown is diethyl phosphate by oxidation.
Controlling factors and toxicokinetic modeling of antibiotics bioaccumulation in aquatic organisms: A review
Published in Critical Reviews in Environmental Science and Technology, 2023
Minghua Zhu, Jingwen Chen, Willie J. G. M. Peijnenburg, Huaijun Xie, Zhongyu Wang, Shuying Zhang
Biotransformation is a vital process that decreases concentrations of parent compounds in an organism (Fu et al., 2020). It was observed that biotransformation greatly reduced the bioaccumulation potential of enrofloxacin in Scophthalmus maximus, Penaeus vannamei, Penaeus japonicus, and A. japonicus (Zhang et al., 2021b; Zhu et al., 2020). Many previous studies also identified the metabolites of antibiotics in aquatic organisms (Liu et al., 2014a, 2014b; Zhao et al., 2016).