No two people are alike, and no drug will affect every human body in exactly the same way. In some instances, metabolized xenobiotic agents are more toxic than the original compound. Rat cyp2b1 preferentially biotransformed the secondeluting atropisomers of pcbs 45 and 95 at low substrate concentration ranges. The conditions selected to measure the activity of an enzyme would not be the same as those. By closing this message, you are consenting to our use of cookies. Factors affecting biotransformation pharmaceutical. In general, children require smaller doses than adults. Biotransformation drug metabolism or biotransformation refers to the biochemical enzymatic conversion of a drug to another chemical form. Factors affecting rates of xenobiotic biotransformation.
Start studying phar430 factors affecting biotransformation. Biotransformation of xenobiotics and factors affecting it. Oct 15, 2012 factors affectingbiotransformation of drugs vincy varghese m. Factors affecting rates of xenobiotic biotransformation intrinsic chemical factors extrinsic host factors enzyme induction and inhibition species, strain, genetics gender, age diet and nutrition hepatic injury and other disease states stress circadian rhythms. There is no a sequence of reaction predetermined and is independent of the classification described above. Body compartment size and composition hemodynamics cardiac output, regional blood flow membrane permeability fatwater solubility of drugs. Biotransformation, in fact, is the inactivation of pharmacological action of drugs. This limitation is due to inherent deficiencies in many of the enzymes responsible for catalyzing phase i and phase ii biotransformations. Inhibition of metabolic enzymes inhibits oxidation. Absorption of alcohol from the duodenum and jejunum is more rapid than from the stomach, hence the rate of gastric emptying is an important determinant of the rate of absorption of orally administered alcohol. This process is experimental and the keywords may be updated as the learning algorithm improves. Factors affecting the aqueous biotransformation of chlormadinone acetate to delmadinone acetate by freely suspended cells of arthrobacter simplex atcc 6946 and bacillus sphaericus atcc 805 were. Conversely, an increased rate of metabolism decreases the intensity and duration of action as well as the drugs efficacy.
Metabolites after biotransformation metabolites usually differ considerably from the parent drug with respect to pharmacologic effects and disposition. Phar430 factors affecting biotransformation flashcards. Factors affecting biotransformation pharmaceutical sciences 352. Factors affecting biotransformation pharmaceutical sciences. Biotransformation is significantly affected by a number of factors, these include. Age may affect the efficiency of biotransformation. Body compartment size and composition hemodynamics cardiac output, regional blood flow membrane permeability fatwater solubility of drugs plasma protein binding. Environmental factors aromatic hydrocarbon contained in cigarette smokers act as enzyme inducers. Species difference in metabolic pathway and identification of human cyp isoform responsible for the metabolism of m17055. Chronic alcoholism might lead to enzyme induction as well. Factors affecting drug metabolism online lecture lecturio. Species, strain, and genetic variations risk assessment is often based on responses observed in animals in this regard, there are often significant differences between species in their abilities to metabolize xenobiotics continued. If biotransformation does not occur, drugs may have longer duration of action, and undesired effects are observed along with desired ones.
Absorption may occur through the alimentary tract, skin, lungs, via the eye, mammary gland, or uterus, as well as from sites of injection. Many factors may affect drug metabolism, and they are discussed in the following sections. The final section of this chapter summarises the effects of external. Many tissues in the body are capable of metabolizing drug,but most drugs are mainly metabolized in the liver by enzymes localized in hepatic microsomes. Drug biotransformation an overview sciencedirect topics. Factors affecting biodegradation and bioremediation in soil, water or air. Studies on the metabolic fate of m17055, a novel diuretic 4.
Thomaspassananti compared to laboratory animals, humans are extremely heterogeneous with respect to the many factors thatcaninfluence thedistribution andbiological effects oftoxic chemicals. The biotransformation of every pollutant could be catalyzed by different enzymes depending on organism. The rate of metabolism increases as enzyme induction takes place. Pdf biotransformation is a process by which organic compounds are. Phar430 factors affecting biotransformation quizlet.
In pharmacology, bioavailability is a subcategory of absorption and is the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. Biodegradation and bioremediation of organic pesticides. Biotransformation of drugs to polar metabolites is a key step in the termination of action and the elimination of drugs used in therapeutics. Biotransformation study guide by cadco25 includes 74 questions covering vocabulary, terms and more. Study 7 factors affecting biotransformation flashcards from stephanie l. The individual makeup of each person causes slight differences in processes like biotransformation. R pohorecki, w rayburn, w w coon and e f domino drug metabolism and disposition may 1. Factors affecting the biotransformation of chlormadinone. Either youngs formula based on age or clarks formula based on weight can be used for calculating the doses for children but the formula based on body surface area is more reliable. Some chemicals are reactive enough to form glutathione adduct without the assistance of gsh transferase. Most of the time cytochrome p450 is involved leading to increased synthesis of new enzymes. Factors affecting the biotransformation of the pesticide. Metabolism or biotransformation of toxicants by the body is an attempt to detoxify.
Because most drugs are metabolized in the liver, attention is centered on factors influencing hepatic drug biotransformation. Factors surrounding the administration of medications may also cause differences in peoples response to drugs. At high altitude decreased biotransformation occurs due to decreased oxygen leading to decreased oxidation of drugs. In general, human fetuses and newborns have limited abilities to carry out xenobiotic biotransformations. Biotransformation is affected by the species of the test. This work is licensed under a creative commons attributionnoncommercialsharealike license. Factors affecting research results what is the single largest factor affecting research outcomes. If you continue browsing the site, you agree to the use of cookies on this website. Factors affecting the renal excretion of drugs hall, stephen d. List 2 describes some factors which affect the absorption of alcohol. Biotransformation is a process specifically to make agents more polar and excretable. Department of biotechnology, university of new south wales, sydney 2052, australia 1 introduction 2 2 factors affecting lphenyla. In hot and humid climate biotransformation is decreased and vice versa. Factors affecting drug metabolism biotransformation.
Pdf investigation of factors affecting biotransformation. Most are rapidly eliminated and have a little pharmacologic activity, but some play an important role in the effects of the drug. For most drugs, two to fivefold differences in the rate or extent of gastrointestinal absorption can occur, depending on the dosage form. Factors affecting drug action norma nicholson ba, ma. R pohorecki, w rayburn, w w coon and e f domino drug metabolism and disposition may 1, 1989, 17 3 271274. Therefore, moststudies onthe role ofthesefactors in determiningdrugdis. Mar 12, 2020 conversely, an increased rate of metabolism decreases the intensity and duration of action as well as the drugs efficacy. The extent to which an inhibitor affects the metabolism of a drug depends upon factors such as the dose and the ability of the inhibitor. Drug metabolism species difference hepatic drug metabolism purine alkaloid drug biotransformation.
Genetic and environmental factors affecting host responseto drugs and other chemical compounds in ourenvironment byelliot s. The existence of different biotransformation pathways can usually explain what causes this doserelated difference in biotransformation. Investigation of factors affecting biotransformation of phytosterols to 9 hydroxyandrost4ene3,17dione based on the hp. Factors affecting the renal excretion of drugs stephen hall. The absorption, distribution, and excretion of drugs objectives after studying this chapter, the reader should be able to. A large number of factors, including infection, alter the basal rates of drug metabolism and cause a number of untoward effects and drug interactions. These results suggest that binding of parathion to bsa hinders its biotransformation by mouse livers perfused in situ, probably by limiting the availability of free pesticide to metabolic sites. Department of pharmacology, sir charles tupper medical building, dalhousie university. Pdf investigation of factors affecting biotransformation of.
List two physiologic factors that can alter each of the processes of absorption, distribution, and excretion. Factors affecting metabolism 2 a balanced diet will provide the necessary protein as well as essential metals and minerals such as copper, zinc, and calcium to assist normal cellular enzymatic activities associated with biotransformation. It includes absorption, metabolism and food effect of drugs. At low doses, a xenobiotic may follow a biotransformation pathway that detoxifies the substance. You can have competitive inhibition of cytochrome p450. Pdf the role of biotransformation in drug discovery and. Explain the meaning of the terms absorption, distribution, metabolism, and excretion. Factors affecting the biotransformation of the pesticide parathion by the isolated perfused mouse liver. Species, strain, and genetic variations risk assessment is often based on. When drugs given over prolonged period of time, upregulation of enzymes takes place. These keywords were added by machine and not by the authors. Environmental affecting host response to drugs compounds. Factors that influence drug biotransformation springerlink.
Factors affecting bioavailability global events usa. Each human being, except for persons whoare one of a set of identical twins ortriplets, is uniquewithrespect to manyenvironmental andgenetic factors that could influence drugdisposition. Factors affecting the biotransformation of trimethylammonium compounds into lcarnitine by escherichia coli. Genetic and environmental factors affecting drug disposition. Factors affecting biotransformation of drugs slideshare. So all of these things are going to affect the way that we metabolize our drugs. Describe the physicochemical and physiological factors that influence the absorption of drugs from enteral and parenteral routes of administration, their distribution within the body, and their routes and mechanisms of elimination. Factors affecting metabolism 1 the rate at which metabolism of toxic substances occurs is dependent on a variety of factors that can be categorized into two groups. However, if the amount of xenobiotic exceeds the specific enzyme capacity, the biotransformation pathway is. Biotransformation of drugs to polar metabolites is a key step in the. Some factors affecting phencyclidine biotransformation by human liver and placenta. Quizlet flashcards, activities and games help you improve your grades. You can inhibit pglycoprotein and you can alter blood flow.
These two characteristics, rate and completeness of absorption, comprise bioavailability. Review case studies and model of storage and distribution. Biological factors affecting toxic response diseases acute and chronic liver injury such as hepatitis, cirrhosis, toxic hepatitis, porphyria, and liver tumors will affect the biotransformation. In vitro incubations of rat cytochrome p450 cyp 2b1 isozyme with three chiral polychlorinated biphenyl pcb congeners pcbs 45, 95, and 2 were performed to investigate factors affecting phase i stereoselective biotransformation. Investigation of factors affecting biotransformation of phytosterols to 9hydroxyandrost4ene3,17dione based on the hp. Pesticides or organophosphate insecticides may act as enzyme inducers. Some people have very unusual drug reactions that may be linked to genetic factors. Factors affecting enzyme activity knowledge of basic enzyme kinetic theory is important in enzyme analysis in order both to understand the basic enzymatic mechanism and to select a method for enzyme analysis. There are many recent advances and factors affecting bioavailability. Factors affecting drug biotransformation sciencedirect. Factors affecting biotransformation of drugs physicochemical properties of the drug chemical factors 1 enzyme induction 2 enzyme inhibition 3 environmental chemicals biological factors 1 strain differences 5 species differences 2 sex differences 6 age 3 diet 7 altered physiologic factors 4 temporal factors. Read factors affecting the biotransformation of trimethylammonium compounds into l carnitine by escherichia coli, biochemical engineering journal on deepdyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips.
Renton department of pharmacology, sir charles tupper medical building, dalhousie university, halifax, ns, canada biotransformation of drugs to polar metabolites is a key step in the termination of action and the elimination of drugs used in thera peutics. Indiana universitypurdue university at indianapolis, indianapolis, in, united states. Large interindividual variations in drug response can arise from multiple genetic and environmental factors affecting drug absorption, distribution, biotransformation, excretion, interaction with receptor sites, or combinations of these. Biotransformation is significantly affected by a number of factors, these. Renal disease can cause disturbances in excretion of a chemical thus increasing its toxicity.
The basis of toxicology involves the absorption, distribution, metabolism, and excretion adme of a toxicant. What are the factors affecting the dose and action of drugs. Enzyme induction xenobiotics induce metabolism of its own autometabolism or other drugs by binding to nuclear receptor and activating expression of target genes by transcription laurence l. Toxic effects may be local, but the toxicant must be dissolved and absorbed to some extent to affect the cell. O factors affecting drug metabolism pharmaceutical chemistry. In the first chapter, the principles underlying drug absorption, distribution, metabolism and elimination are described, with drug metabolism highlighted within the context of these fundamental processes.
Principles of environmental toxicology 3 absorption distribution absorption through skin, lung or intestinal tissue is. Absorption, distribution, metabolism, and excretion. Factors affecting phase i stereoselective biotransformation. These include age, species and strain, genetic or hereditary factors, sex, enzyme induction, and enzyme inhibition.
Well you have genetic differences of cytochrome p450. Proteindeficient diets can result in a decrease in protein. Principles of pharmacokinetics learning objectives. Nakajima h, nakanishi t, nakai k, matsumoto s, ida k, ogihara t, ohzawa n. It can play an important role in identifying factors underlying the. Whatamidoingthatmayimpactthe laboratory also sharing this holding room. Sonam biotransformation biotransformation of drugs is nothing but the chemical. This work is licensed under a creative commons attribution. Genetic and environmental factors affecting drug disposition in man. Learn vocabulary, terms, and more with flashcards, games, and other study tools. The rate of drug biotransformation depends on numerous variables, including access to the site of metabolism, the concentration and phenotype of the enzyme present, and the effect of certain agents on enzymatic activity. Factors affecting biotransformation pharmaceutical sciences 352 with surrattharrold at duquesne university studyblue. To learn about our use of cookies and how you can manage your cookie settings, please see our cookie policy. Some factors affecting phencyclidine biotransformation by.
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