Microorganisms possess the capability to enzymatically modify a wide range of organic compounds. Factors affecting rates of xenobiotic biotransformation. Proteindeficient diets can result in a decrease in protein. Production of metabolites that are more polar than the parent drug usually terminates the pharmacologic action of the parent drug after phase i reactions, similar or different pharmacologic activity, or toxicologic activity. Biotransformation may convert drugs to active metabolites or inactive sometimes toxic metabolized products. A large number of factors, including infection, alter the basal rates of drug metabolism and cause a number of untoward effects and drug interactions. Factors affecting biotransformation of drugs slideshare.
Biotransformation of drugs biochemical modification degradation of drugs drugs are partially eliminated unchanged or partially biotransformed by metabolic pathways and are excreted as metabolites biotransformation of drugs influences the deactivation, activation, detoxification, and toxification of the vast majority of drugs 2. Factors affecting biotransformation pharmaceutical sciences. Drug biotransformation an overview sciencedirect topics. Because most drugs are metabolized in the liver, attention is centered on factors. Various factors affecting the bioavailability of drugs following oral administration, viz. These bioremediation and biotransformation methods harness the naturally occurring, microbial catabolic diversity to degrade, transform or accumulate a huge range of compounds including hydrocarbons e. Many factors affect the rate and pathway of metabolism of drugs, and the major. Biotransformation is catalyzed by specific enzyme systems.
Biotransformation is a major mechanism for drug elimination. In general, human fetuses and newborns have limited abilities to carry out xenobiotic biotransformations. Pdf significance of biotransformation in drug discovery and. Types of factors chemical biological altered physiological temporal route of drug administration enviornmental 3. Biotransformation of drugs to polar metabolites is a key step in the termination of action and the elimination of drugs used in therapeutics. Test your expertise of the subject with a printable worksheet and an interactive quiz. Biotransformation is significantly affected by a number of factors, these include. Department of pharmacology, sir charles tupper medical building, dalhousie university. Factors affecting drug biotransformation sciencedirect. As such, the term is generally used to refer to hepatic metabolism of drugs, but could in fact apply to various other settings. 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. Distribution process is carried out by the circulation of blood, one of the compartment is always the blood or the plasma and the other.
The effects of food on the absorption of drugs and the molecular basis by which dietary chemicals affect drug metabolism are discussed. Permission has been granted for its use in this blog. Decreased intensity and duration of action of drugs e. This limitation is due to inherent deficiencies in many of the enzymes responsible for catalyzing phase i and phase ii biotransformation. 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. Read this article to learn about the types and techniques of biotransformations and its product recovery. Tissue characteristics and developmental age strongly influence enzyme expression. Pdf overview of factors affecting oral drug absorption. Ppt biotransformation powerpoint presentation free to. In this chapter, we discuss the interactions of food and drugs.
Oct 15, 2012 factors affectingbiotransformation of drugs vincy varghese m. Although phase i drug metabolism occurs in most tissues, the primary and first pass site of metabolism occurs during hepatic circulation. Ravindran s, basu s, surve p, lonsane g, sloka n 2012 signi cance of biotransformation in drug discovery and development. Because most drugs are metabolized in the liver, attention is centered on factors influencing hepatic drug biotransformation. Start studying absorption of drugs distribution of drugsbiotransformation. Biotransformation of various pollutants is a sustainable way to clean up contaminated environments. However, there is growing evidence that most common drugmetabolizing enzymes are expressed in the skin. If you continue browsing the site, you agree to the use of cookies on this website.
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. The of the text is held by trustees of boston university. Although it is the largest organ of the human body, skin is often not considered in discussions of drug metabolism. Factors affecting metabolism request pdf researchgate. The process takes place through an interaction of substrates with the. It is also striking that high dose drugs, administered to patients at doses of 100 mg per day or greater, tend to be the ones which most frequently cause liver injury, while low dose drugs given at 10 mg per day or less rarely are problematic in this regard 11,12. Others include git, lungs, kidneys, skin, adrenals and blood plasma. Pharmaceutic factors affecting drug bioavailability toxicology. Drugs can be eliminated from the systemic circulation unchanged by renal excretion e. Biotransformation drug metabolism or biotransformation refers to the biochemical enzymatic conversion of a drug to another chemical form. Factors affecting biotransformation of drugs physicochemical properties of the drug chemical factors 1 enzyme induction 2 enzyme inhibition. Biotransformation of drugs in human skin drug metabolism.
For this reason, optimization of lead compounds in drug discovery programs. Factors effecting bioavailability studies bodavula samba siva rao department of pharmacy, khammam college of pharmacy, khammam, andhra pradesh the goal of most oral dosage forms is to serve as a vehicle for the delivery of drugs to the blood stream for distribution to the site of action. Age may affect the efficiency of biotransformation. Prodrugs may have advantages over the active form as more stable, having better bioavailability or less side effects and toxicity. The influencing factors are of physiological, pathological, or external origin.
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. 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. When drugs given over prolonged period of time, upregulation of enzymes takes place. Biotransformation is a handy term which describes the latter.
Biotransformation of drugs to polar metabolites is a key step in the. Biotransformation is a major mechanism for drug toxin elimination. Biotransformation and metabolism of drugs deranged physiology. Biotransformation of drug is defined as the conversion from one chemical form to another. The biochemistry of drug metabolism an introduction request pdf. Biotransformationmetabolism excretion the interrelationship between drug distribution, bio transformation and excretion and the drug in figure 1. Factors that influence drug biotransformation springerlink. Us food and drug administration 2008b center for drug evaluation and research, table of valid genomic biomarkers in the context of approved drug labels.
Biotransformation is the metabolic process by which the liver alters or modifies substances entering the body, such as drugs. Phase i biotransformation reactions introduce or expose functional groups on the drug with the goal of increasing the polarity of the compound. 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. Absorption of drugs distribution of drugsbiotransformation. Factors affecting bioavailability global events usa. Other approach to enhance the dissolution and absorption rate of certain drugs is by formation of in situ salt formation i. Some inactive comp are converted to active drugs within the body. Pdf formulation considerations and factors affecting. Biotransformation, in fact, is the inactivation of pharmacological action of drugs. 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. Biotransformation and detoxication are not synonyms. Genetic and environmental factors affecting drug disposition in man.
703 1358 396 747 865 1371 672 1079 547 811 503 997 928 503 765 759 476 241 602 1512 554 361 523 376 1126 1175 811 1262 738 57 830 1318 864 1314 281 596 1277 189 244 920 1499 223 392 1221 692 578