Dressman received february 20, 1996, from the department of pharmaceutics, victorian college of pharmacy, monash university. Once a drug molecule has passed through to the basolateral side of the intestinal epithelium, absorption into the blood is generally not restricted. 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. Atorvastatin is a selective, competitive inhibitor of hmgcoa reductase, the rate. Lipid water solubility coefficient is the ratio of dissolution of drug in lipid as compared to water. D distribution transporters m metabolism tannenbaum hoffmaster. In this study, we investigated the mechanism of paclitaxel absorption after oral administration of dhp107 in mice and rats by changing the dosing interval, and.
For drugs applied at their target, such as local anesthetics. Cation inhibition of active sugar transport and 22na influx into hamster small intestine, in vitro. Qureshi, predicting absorption characteristics of drugs october 30, 2012 page 1 absorption mechanism of drugs from the gi tract. Factors affecting bioavailablililty and absorption of drugs and drug. Mechanism of gastrointestinal drug absorption and application in. 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.
Greater the lipid water solubility coefficient, more is the lipid solubility of the drug and greater is the absorption. Drug mechanism copyright 2018 transcellular stomach. For absorption into the cells, a drug must traverse the cell membrane. The mechanism of absorption is shown to be compound specific, transcellular, and without any evidence of effect on tight junctions. Percutaneous absorption and schaefer et al skin permeability. The journal will accept original submissions in english on the understanding that the work is unpublished and is not being considered for publication elsewhere. The book evolved from the reports presented at the. Only a few drugs move across cellular barriers in an active way. Explain the meaning of the terms absorption, distribution, metabolism, and excretion. Strategies to enhance drug absorption via nasal and. The process of movement ofunchanged drug from the site of administration to systemic circulation. The process of movement ofunchanged drug from the site of.
The two paracellular transport mechanisms involved in drug absorption are permeation through tight junctions of epithelial cells this process basically occurs through openings which are little bigger than the aqueous pores. Drug absorption is determined by the drug s physicochemical properties, formulation, and route of administration. A drugs dissolve rapidly in the alkaline medium whereas w. Absorption of drugs from the gastrointestinal tract.
In this process, the fraction dose absorbed is determined by the membrane permeability. For drug absorption to occur, a drug must cross biologic barriers e. Review article physicochemical and physiological mechanisms for the effects of food on drug absorption. Swift, md, phd professor, department of psychiatry and human behavior. Mechanisms of drug absorption and distribution annual. With oral administration, several factors affect the absorption of a drug. Absorption can be defined as the movement of active drug or prodrug from the site of administration. Introduction to various mechanisms of absorption of drugs. In the present study, a bcs class iv drug and a pglycoprotein pgp substrate, morin, was selected as the model drug to elucidate the oral absorption mechanism of plcsnedds.
Topical drugs, the mainstay of treatment in dermatology, are applied in the hope and expectation that any percutaneous absorption will be minimal and that systemic side effects will not occur. List two physiologic factors that can alter each of the processes of absorption. For example, ginkgo biloba may increase the effect of anticoagulants. Additional evidence that it is mainly the nonionized form of a drug which is absorbed was obtained by changing the degree of ionization of drugs by raising the ph. Some drugs, notably insulin, are routinely administered sc. Mechanisms of drug absorption and excretion annual. 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. Biochimica et biophysica acta bba biophysics including photosynthesis 1965, 102 2, 423435.
Pdf overview of factors affecting oral drug absorption. Physiological factors and drug absorption pharmacokinetics. On the mechanism of absorption of drugs from the gastrointestinal. Pharmacology and pharmacokinetics of alcohol and opioids understanding the drugs robert m. Principles of pharmacokinetics learning objectives. This figure evidence that for a drug absorbed by passive diffusion, the rate of absorption increases in a linear relationship to drug concentration. Here, a carrier protein moves molecules against the conc. Tufts health care institutes program on opioid risk management.
In order to gain an insight into the numerous factors that can potentially influence the rate and extent of drug absorption into the systemic circulation, a schematic. If drugs are absorbed by passive diffusion through a lipoid membrane, their rate of absorption. The anatomy and physiology of the drug absorption site. Introduction transport of drug across biological barriers for systemic absorption, a drug must pass from the absorption site through one or more layers of cells to gain access into the general circulation. 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. The ultimate goal of drug absorption is to have the drug reach the site of action in a concentration which produces a pharmacological effect. Drug mechanism transcellular stomach absorption of a derivatized. It will interest those who are concerned with transdermal drug delivery and toxicology. Some other factors which significantly affect the drug absorption are the type of mechanism involved in absorption and gastrointestinal physiology such as gi. A comparison between the rate of drug absorption and the concentration of drug at the absorption site is shown in fig. The factors affecting absorption of drugs are related both to the drugs and to the body factors related to drugs.
Drug absorption is the movement of a drug from its site of application into the bloodstream. Accordingly the unionized form of an acid or basic drug, if sufficiently lipid soluble, is absorbed but the ionized form is not. Depending on drug pka and whether it is acidic or basic, absorption depends on the amount of unionised form at site of absorption. Absorption distribution dose of drug pharmacological effect drug at active site drug in blood i n p u t l o s s. This may result in a change in the rate of absorption or extent of drug absorption or both. 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. Absorption passage of compound from the site of administration into the bloodstream or lymph, usually across a membrane. Lipidsoluble drugs dissolve in the membrane, and are driven through by a. Mechanisms of oral absorption improvement for insoluble. Intravenous administration does not involve absorption and, hence, there is no loss of drug.
Carrier proteins, ion channels are required for this type of diffusion. Drug absorption merck manuals professional edition. Pdf impact of physiological, and biopharmaceutical. 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.
Studies on the mechanism of intestinal absorption of sugars viii. 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. Evaluation of skin absorption of drugs from topical and. Absorption can be facilitated by heat, massage or vasodilators. Most soluble drugs are absorbed via passive diffusion. Drug absorption is a pharmacokinetic parameter that refers to the way a drug is absorbed from a pharmaceutical formulation into the bloodstream. Phospholipid complex plc based selfnanoemulsifying drug delivery system plcsnedds has been developed for efficient delivery of drugs with poor solubility and low permeability. In the present study, a water insoluble drug named silybin was encapsulated into selfnanoemulsifying drug delivery system snedds following the preparation of silybinphospholipid complex sbpc, then several methods were carried out to characterize sbpcsnedds and elucidate its mechanisms to improve the oral absorption of sb. Pharmacology and pharmacokinetics of alcohol and opioids. Physiological factors influencing oral drug absorption. The absorption, distribution, and excretion of drugs objectives after studying this chapter, the reader should be able to. Absorption and mechanism of transport of drug across cell. Gastrointestinal tract physiology and drug absorption.
Recently, an altered chloroquinetransporter protein cg2 of the parasite has been related to chloroquine resistance, but other mechanisms of resistance also appear to be involved. Absorption mechanism of dhp107, an oral paclitaxel. 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. Lipitor tablets for oral administration contain 10, 20, 40 or 80 mg atorvastatin and the. Passive permeability and transportermediated mechanisms coexist to impact drug absorption and disposition aa pept1 concentration gradient mw drugs requires the use of transporters.
Brown university medical school associate chief of staff for research va medical center providence, ri. The rate of passive absorption of weak electrolyte is related to the fractions of the total drug that exists in the unionized form in solution in the gi fluids at the absorption. The drug molecule combine with carrier protein and then it transferred drug to the other side of membrane, there it leaves the molecule and come back to normal situation or form. It can be slowed by coadministration of vasoconstrictors, a practice commonly used to prolong the local action of local anesthetics. Passive lipid diffusion is probably the most important absorptive mechanism. Physicochemical and physiological mechanisms for the. Drug metabolism and pharmacokinetics journal elsevier. Impact of physiological, and biopharmaceutical factors in absorption and metabolism mechanisms on the drug oral bioavailability of rats and humans. Drug herb or supplement interactions occur when an herb or dietary supplement changes the expected effect of a drug. 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. For optimum absorption, the drug should have sufficient aqueous solubility to dissolve in the. 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. Intravascular placement of the drug directly into blood intravenous iv or intraarterial.
Extravascular oral, sublingual, subcutaneous, intramuscular, rectal. Rectal drug delivery, rectal absorption, suppositories. Drug absorption is generally slower sc than im, due to poorer vascularity. In addition to transcellular permeation, drugs can be absorbed by a paracellular mechanism, and the tight junction structure represents the barrier to paracellular absorption.
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