In order to develop a drug product that elicits the desired therapeutic objective, the pharmaceutical scientist must have a thorough understanding of the biopharmaceutic properties of the drug and drug product and the physiologic and pathologic factors affecting drug absorption from the application site. The chemical composition of a drug, as well as the environment into which a drug is placed, work together. Absorption distribution dose of drug pharmacological effect drug at active site drug in blood i n p u t l o s s. Studies with microscopically visible tracers such as small proteins and dextrans suggest that the major pathway across stratified epithelium of large. Drug herb or supplement interactions occur when an herb or dietary supplement changes the expected effect of a drug. Jan 24, 2019 absorption is the process of a drug moving from its site of delivery into the bloodstream. Overview of factors affecting oral drug absorption. The glucose is transported along with sodium from the git membrane. Each beadfilled focalin xr capsule contains half the dose as immediaterelease beads and half as entericcoated, delayedrelease beads, thus providing an immediate release of dexmethylphenidate and a second delayed release of dexmethylphenidate.
The main mechanism for the absorption of the drug in to oral mucosa is via passive diffusion into the lipoidal membrane3. Mechanism of action and pharmacology vyvanse is a pro drug of dextroamphetamine. Dosage forms eg, tablets, capsules, solutions, consisting of the drug plus other ingredients, are formulated to be given by various routes eg, oral, buccal, sublingual, rectal. Increase in drug penetration by iontophoresis can be due to following mechanisms. Ideally a drug should have sufficient aqueous solubility to dissolve in the fluids at absorption site sufficient lipid. Passive permeability and transportermediated mechanisms coexist to impact drug absorption and disposition aa pept1 concentration gradient mw drugs requires the use of transporters. Drugs are most often administered to man by the oral route. Pdf overview of factors affecting oral drug absorption. Drug metabolism and pharmacokinetics journal elsevier. Unless a drug is directly applied to, or in the vicinity of, the target site, absorption must occur for a drug to exert its therapeutic effect. Passive lipid diffusion is probably the most important absorptive mechanism.
The problem of enzymatic degradation by concentrating an absorption sites is free digestive enzymes. Intravascular placement of the drug directly into blood intravenous iv or intraarterial extravascular oral, sublingual, subcutaneous, intramuscular, rectal. Anionic drugs can cross the skin by using a negatively charged working electrode. Explain how bioavailability can impact drug response and product selection.
Absorption of drugs from the gastrointestinal tract. A drugs dissolve rapidly in the alkaline medium whereas w. Accordingly the unionized form of an acid or basic drug, if sufficiently lipid soluble, is absorbed but the ionized form is not. It also occurs by subcutaneous, intra muscular and transdermal routes of administration of drugs.
It can be slowed by coadministration of vasoconstrictors, a practice commonly used to prolong the local action of local anesthetics. Goals of drug absorption and bioavailability lecture. Drug absorption is generally slower sc than im, due to poorer vascularity. Physiologic factors related to drug absorption applied. Mechanisms of drug absorption and distribution annual. On the other hand, for drugs absorbed in the stomach, delayed. Advise parents or caregivers to check concentrations of liquid.
Physicochemical and physiological mechanisms for the effects of food on drug absorption. The chemical composition of a drug, as well as the environment into which a drug is placed, work together to determine the rate and extent of drug absorption. Unless a drug is directly applied to, or in the vicinity of, the target site, absorption must occur for a drug to exert its therapeutic. Biopharmaceutics classification system is proved to be a successful predictive tool for drug development. Baclofen is rapidly and extensively absorbed and eliminated. Pdf impact of physiological, and biopharmaceutical.
If sustained or controlledrelease drug delivery systems are being designed, it is important to consider factors that will affect their behaviour and, in particular. May 01, 2010 ocular drug delivery has been a major challenge to pharmacologists and drug delivery scientists due to its unique anatomy and physiology. The rate and extent of rectal drug absorption are often lower than with oral absorption possibly an inherent factor owing to the relatively small surface area available for drug uptake. Spironolactone mechanisms of drug food interactions pharmacokinetic interactions drug absorption interactions food may affect drug absorption in the gi tract by altering gastric ph, secretion, gastrointestinal motility and transit time. But it depends on the amount of carriers by which the drug molecules can be bound. Significance rating a criteria management rating b criteria.
Physiological factors and drug absorption pharmacokinetics. This figure evidence that for a drug absorbed by passive diffusion, the rate of absorption increases in a linear relationship to drug concentration. If drugs are absorbed by passive diffusion through a lipoid membrane, their rate of absorption. Drug metabolism and pharmacokinetics dmpk is an official online journal of the japanese society for the study of xenobiotics jssx, and it replaces the jssxs former journal, xenobiotic metabolism and disposition. In this case also the carrier proteins are required, but transfer is occurred due to absorption of other molecule, which facilitate movement of drug molecule. Absorption passage of compound from the site of administration into the bloodstream or lymph, usually across a membrane systemic routes of drug administration. Only a few drugs move across cellular barriers in an active way.
Sodas spheroidal oral drug absorption system technology. The process of movement ofunchanged drug from the site of administration to systemic circulation. Ph partition theory of drug absorption is based on the assumption that the git is a simple lipid barrier to the transport of drugs and chemicals. Compared to other modes of administration, this route is unusually difficult to describe with regard to the physicochemical conditions existing at the site of absorption. For example, highfiber foods and calcium supplements may bind with a drug and prevent it from being absorbed. Baclofen fda prescribing information, side effects and uses.
It is very likely that these will be the site of drug drug interactions although most are uncharacterised. Peff and predict the plasma pharmacokinetic profile. Pdf impact of physiological, and biopharmaceutical factors. Phenytoin is an antiepileptic drug which can be useful in the treatment of epilepsy. Lipidsoluble drugs dissolve in the membrane, and are driven through by a. Static barriers different layers of cornea, sclera, and retina including blood aqueous and bloodretinal. Explain the meaning of the terms absorption, distribution, metabolism, and excretion.
There appears to be a good correlation between in vitro and in vivo permeability for drugs with passive diffusion as the main transport mechanism, but there is a significant deviation for drugs absorbed through transporters. Dosage forms eg, tablets, capsules, solutions, consisting of the drug plus other ingredients, are formulated to be given by various routes eg, oral, buccal, sublingual, rectal, parenteral, topical, inhalational. Sustained release drug delivery system works on many different mechanisms to control the release rate of drugs. In this process, the fraction dose absorbed is determined by the membrane permeability. Compare the roles of passive diffusion and carriermediated transport in drug absorption. Percutaneous absorption and schaefer et al skin permeability. After oral administration, lisdexamfetamine dimesylate is rapidly absorbed from the gastrointestinal tract and converted to dextroamphetamine, which is responsible for the drug s activity. 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. Studies on the mechanism of intestinal absorption of sugars viii. Some drugs, notably insulin, are routinely administered sc. For drugs applied at their target, such as local anesthetics, absorption often terminates the therapeutic effect.
This videos provides an overview of drug absorption, with a look at oral vs intravenous administration. The primary site of action appears to be the motor cortex where spread of seizure activity is inhibited. Describe two types of drug interaction and explain how they might affect drug response and safety. The journal will accept original submissions in english on the understanding that the work is unpublished and is not being considered for publication elsewhere. Learn vocabulary, terms, and more with flashcards, games, and other study tools. Rectal drug delivery, rectal absorption, suppositories. Thus by understanding the physicochemical properties of a compound and by recognizing the. It will interest those who are concerned with transdermal drug delivery and toxicology. Mechanisms of drug absorption authorstream presentation. However, the absorptive process does not occur during direct injection of drug by intravenous or intra arterial injection. Once a drug molecule has passed through to the basolateral side of the intestinal epithelium, absorption into the blood is generally not restricted.
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. It is known that the small intestine is the major site of drug absorption, and thus the time a drug is present in this part of the gastrointestinal tract is extremely important. Drug absorption is the movement of a drug from its site of application into the bloodstream. The factors that influence the rate and extent of absorption depend upon the route of administration. For example, ginkgo biloba may increase the effect of anticoagulants. Some other factors which significantly affect the drug absorption are the type of mechanism involved in absorption and gastrointestinal physiology such as gi. The absorption of the drug through the sublingual route is 3 to 10 times greater than oral route and is only surpassed by hypodermic injection. Physicochemical and physiological mechanisms for the effects. Physicochemical and physiological mechanisms for the. Simple diffusion diffusion directly through lipid facilitated diffusion carrier mediated active transport carrier mediated pinocytosis drinking of cell simple diffusion. Oral drug bioavailability can also be markedly influenced by physiological factors, such as gastrointestinal. Vyvansetm lisdexamfetamine dimesylate c ii rx only. Cation inhibition of active sugar transport and 22na influx into hamster small intestine, in vitro.
Baclofen is excreted primarily by the kidney in unchanged form and there is relatively large intersubject variation in absorption andor elimination. The effects are potentially lifethreatening or capable of causing permanent damage. For drug absorption to occur, a drug must cross biologic barriers e. Absorption of drugs pharmacokinetics pharmacology lect 2. Developing oral sustained release matrix tablets for drug with constant release rate has always. This tutorial discusses routes of administration and how th. Mechanism of gastrointestinal drug absorption and application in. The absorption, distribution, and excretion of drugs objectives after studying this chapter, the reader should be able to.
The passive transport of nonionic species across the lipid membrane of the buccal cavity is the. Impact of physiological, and biopharmaceutical factors in absorption and metabolism mechanisms on the drug oral bioavailability of rats and humans. Drug absorption merck manuals professional edition. Pharmacokinetic part 01 absorption and factors affecting. Jun 19, 2019 drug absorption is a pharmacokinetic parameter that refers to the way a drug is absorbed from a pharmaceutical formulation into the bloodstream. Dressman received february 20, 1996, from the department of pharmaceutics, victorian college of pharmacy, monash university. Mechanism of absorption of drug by four ways the drug can be migrated. Pharmacodynamics basic notes pdf ppt atropine furosimide. Most soluble drugs are absorbed via passive diffusion. The cellular membrane consists of a double layer of amphiphilic phospholipid molecules, their hydrocarbon chains are oriented inwards to form the hydrophobic or lipophilic phase and their polar heads oriented to form inner hydrophilic boundaries of the cellular membrane that face the. Delayed gastric empty ing may decrease the absorption of drugs normally absorbed in the small intestines, because increased transit time from the stomach can lead to degradation. Principles of pharmacokinetics learning objectives. On the mechanism of absorption of drugs from the gastrointestinal.
There are many gi absorption models that investigate transport mechanisms, determine the. Gastrointestinal tract physiology and drug absorption. Laxatives and diarrhea, which speed up the passage of substances through the digestive tract, may reduce drug absorption. Route onset peak duration acetaminophenoral,rectal. The drug transport mechanism through the buccal mucosa involves two major routes. Pharmacokinetics, pharmacodynamics, and pharmacogenomics. Food can influence the absorption of drugs by different mechanisms. Review article physicochemical and physiological mechanisms for the effects of food on drug absorption. Absorption can be facilitated by heat, massage or vasodilators.
Drug absorption is determined by the drugs physicochemical properties, formulation, and route of administration. Drug transport systems, notably the pglycoprotein the product of the multidrug resistance gene, are responsible for limiting or enhancing absorption of drugs. Sustained release oral drug delivery system an overview. Sep 29, 2012 the majority of drug are administeredextravascularly generally orally the drug can exerts their pharmacologicalaction when they come in to bloodcirculation from their site of application,and for this absorption is an important step drug absorption is defined as the processof movement of unchanged drug from thesite of administration to systemic. List two physiologic factors that can alter each of the processes of absorption. Several factors can affect the absorption of a drug into the body.
Food, other drugs, and digestive disorders can affect drug absorption and bioavailability. Warfarin drug interactions anticoagulation services. Introduction to various mechanisms of absorption of drugs. The book evolved from the reports presented at the. Jul 03, 20 this tutorial is the second in the pharmacokinetics series. Drug absorption is determined by the drug s physicochemical properties, formulation, and route of administration. It is not surprising then that investigators interested in the mechanisms of gastrointestinal absorption have largely turned to surgically prepared laboratory animals in which one portion of the gastrointestinal tract can be studied at a time, the nature of the luminal contents controlled, and drugs maintained in true aqueous solution. Drug administration often the goal is to attain a therapeutic drug concentration in plasma from which drug enters the tissue therapeutic window between toxic concentration and minimal effective concentration.
It is usually associated with oral drugs and their absorption through the git. The process of movement ofunchanged drug from the site of. Depending on drug pka and whether it is acidic or basic, absorption depends on the amount of unionised form at site of absorption. A comparison between the rate of drug absorption and the concentration of drug at the absorption site is shown in fig. Drug absorption is a pharmacokinetic parameter that refers to the way a drug is absorbed from a pharmaceutical formulation into the bloodstream. This may result in a change in the rate of absorption or extent of drug absorption or both. Biochimica et biophysica acta bba biophysics including photosynthesis 1965, 102 2, 423435. Brodie proposed the ph partition theory to explain the influence of gi ph and drug pka on the extent of drug transfer or drug absorption. Mechanisms of drug absorption and excretion annual. Evaluation of skin absorption of drugs from topical and. In addition to transcellular permeation, drugs can be absorbed by a paracellular mechanism, and the tight junction structure represents the barrier to paracellular absorption. In fact, most drug absorption occurs in the small intestine. As stated in chapter 18, the intravenous route offers direct access to the systemic circulation and the total dose administered via this route is available in the plasma for distribution into other body tissues and the sites of action of the drug.
The cellular membrane consists of a double layer of amphiphilic phospholipid molecules, their hydrocarbon chains are oriented inwards to form the hydrophobic or lipophilic phase and their polar heads oriented to form inner hydrophilic boundaries of the cellular membrane that face the surrounding aqueous. Absorption may be dosedependent, being reduced with increasing doses. Mechanism of buccal absorption17 buccal drug absorption occurs by passive diffusion of the nonionized species, a process governed primarily by a concentration gradient, through the intercellular spaces of the epithelium. Absorption is the process by which drug molecules cross biological membranes.
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