It is the measure of the rate kinetics of absorption, distribution, metabolism and excretion adme. Termination of effect, metabolism andor elimination what does kinetic or kinetics refer to. Before a drug can be absorbed after oral administra tion it has to pass through a number of stages, illustrated in figure 1. Pdf prediction of drug absorption using multivariate. Absorption and drug development wiley online books. Absorption enhancing excipients in systemic nasal drug.
In such cases, systemic absorption is a prerequisite for efficacy. Static barriers different layers of cornea, sclera, and retina including blood aqueous and bloodretinal barriers, dynamic barriers choroidal and conjunctival blood flow, lymphatic clearance, and tear dilution, and efflux pumps in conjunction pose a. Drugdrug interactions can be classified in terms of indirect effects by one drug on gastrointestinal tract physiology influencing the absorption of other drugs, or direct interactions involving altered ph, adsorption, absorption, or chelation. Introduction to pharmacokinetics and pharmacodynamics ashp. However, the pharmacokinetics of drugs used to treat. Mechanistic oral absorption modeling and simulation for formulation development and bioequivalence be evaluation pdf 2. Neonatal absorptionenteral most drugs absorbed in small intestine gastrointestinal ph, transit time, and gastric emptying play important roles in total drug exposure time and absorption gastric acidity does not reach adult levels until 23 years of age introduction of nutrition helps regulate gi function.
At higher drug concentrations the rate of drug absorption remains constant. Most common drug interactions encountered in hiv infection involve those that affect absorption or metabolism. First, the drug needs to be introduced via some route of administration oral, topicaldermal, etc. Describing this phenomenon in an absorption model for in vivo predictions requires an adjustment to the e. First, drug absorption from the site of admin istration permits entry of the compound into the blood stream. Apr 09, 2011 the four processes involved when a drug is taken are absorption, distribution, metabolism and elimination or excretion adme. Factors affecting drug absorption and distribution anaesthesia and. The factors affecting absorption of drugs are related both to the drugs and to the body factors related to drugs. Accordingly the unionized form of an acid or basic drug, if sufficiently lipid soluble, is absorbed but the ionized form is not. Ocular drug delivery has been a major challenge to pharmacologists and drug delivery scientists due to its unique anatomy and physiology. Drug absorption is generally slower sc than im, due to poorer vascularity. Pdf drug absorption, distribution, metabolism and excretion. Absorption and drug development pdf alzaytoonah university. Drug patches drug enters systemic circulation by zero order.
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. However, the absorptive process does not occur during direct injection of drug by intravenous or intra arterial injection. Drug absorption is determined by the drugs physicochemical properties, formulation, and route of administration. Get a printable copy pdf file of the complete article 267k, or click on a page image below to browse page by page. Majority of drugs are administered extravascularly generally orally. The aims of this study were to investigate the absorption mechanisms of rituximab in rats by using slow s. Fairly similar drug solubility has also been shown figure 6 for a number of drugs in human and dog intestinal fluid obtained both under fasting and fed conditions in a recent study.
Drug absorption is determined by the drug s physicochemical properties, formulation, and route of administration. Maggio, et aegis therapeutics llc, san diego, ca usa received. With oral administration, several factors affect the absorption of a drug. The book emphasizes oral absorption, explaining all the physicochemical methods used today to. Formulations can be readily prepared to provide desired release characteristics. Lipid water solubility coefficient is the ratio of dissolution of drug in lipid as compared to water. Physiological factors and drug absorption pharmacokinetics. The availability of a viable oatp2b1deficient mouse model provides an opportunity to unequivocally determine the contribution of this transporter to the absorption and drugdrug interaction potential of drugs. Intravenous administration does not involve absorption and, hence, there is no loss of drug. Drug absorption is the movement of a drug from its site of application into the bloodstream. Ocular drug delivery has been a major challenge to pharmacologists and drug delivery scientists due to. 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. For example, highfiber foods and calcium supplements may bind with a drug and prevent it from being absorbed. The tablets are small in size which is to be used through the sublingual route.
Clinical pharmacokinetics is the application of pharmacokinetic principles to the safe and effective therapeutic management of drugs in. 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. Links to pubmed are also available for selected references. 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. Pdf overview of factors affecting oral drug absorption. Pharmacists must also understand the relationship of drug dosage to therapeutic efficacy.
Pharmacokinetics is the way the body acts on the drug once it is administered. Emphasis is placed upon absorp tion of drugs following oral administration because it illustrates all sources of variability encountered during drug absorption. Amount of drug that exists in unionized form and in ionized form is a function of pka of drug and ph of the fluid at the absorption site, and it can be determined by handersonhasselbach equation. Human absorption, distribution, metabolism and excretion. Once absorbed, the drug may then leave the blood stream and disperse into the tissues and intracellular fluids where it can reversibly bind to receptors. These two characteristics, rate and completeness of absorption, comprise bioavailability. Interactions affecting drug absorption springerlink.
For drugs applied at their target, such as local anesthetics, absorption often terminates the therapeutic effect. Drug absorption clinical pharmacology merck manuals. Dimethyl sulfoxide dmso enhances the percutaneous absorption of many drugs, but its use is controversial because of concerns about its toxicity. 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. It can be slowed by coadministration of vasoconstrictors, a practice commonly used to prolong the local action of local anesthetics. Bioavailability is the percentage of administered drug available in the systemic circulation in respect of route of administration. Generally, the bioavailability of oral drugs follows the order. Use of prescription or overthecounter drugs or medications shown to interfere with nutrient intake or use, to an extent that nutritional status is compromised. Pharmacokinetics also concerns the relationship of the processes to the intensity. In most cases, drugs cross cell membranes by passive dif fusion down a concentration gradient due to random molecular movements produced. Practical approach to modeling the impact of amorphous drug. All critically ill patients require medication to treat organ dysfunction. Pharmacokinetics basics absorption, distribution, metabolism.
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. A drug is injected thus, absorption is an important intravascularly iv or ia prerequisite step directly enters into systemic circulation. Drug absorption is a pharmacokinetic parameter that refers to the way a drug is absorbed from a pharmaceutical formulation into the bloodstream. Rapid absorption with a rapid increase in plasma drug level can be achieved. Absorption can be facilitated by heat, massage or vasodilators. The availability of a viable oatp2b1deficient mouse model provides an opportunity to unequivocally determine the contribution of this transporter to the absorption and drug drug interaction potential of drugs.
Pharmacokinetics is the study and characterization of the time course of drug absorption, distribution, metabolism and excretion. Mechanisms of subcutaneous absorption of rituximab in rats. Such drugs can exert the pharmacological action only when they come into systemic circulation from their site. Intravascular placement of the drug directly into blood intravenous iv or intraarterial extravascular oral, sublingual, subcutaneous, intramuscular, rectal most drugs administered extravascularly act systemically. Drug drug interactions can be classified in terms of indirect effects by one drug on gastrointestinal tract physiology influencing the absorption of other drugs, or direct interactions involving altered ph, adsorption, absorption, or chelation. Compare the roles of passive diffusion and carriermediated transport in drug absorption. It is usually associated with oral drugs and their absorption through the git. Several factors can affect the absorption of a drug. Passage through lipid cell membrane by dissolution in membrane.
Role of oatp2b1 in drug absorption and drugdrug interactions. Clinical pharmacokinetics is the application of pharmacokinetic principles to the safe. However, systemic absorption does occur and varies with the area, site, drug, and state of the skin. First of all, a class i drug is expected to provide complete absorption whereas a certain reduction in bioavailability due to permeability or solubility, as well as due to other reasons e. Greater the lipid water solubility coefficient, more is the lipid solubility of the drug and greater is the absorption. Pharmacokinetic absorption, distribution, metabolism, and excretion adme parameters are today considered to have a crucial role in the selection process of oral candidate drugs for product. Absorption is the process by which drug molecules cross biological membranes. Laxatives and diarrhea, which speed up the passage of substances through the digestive tract, may reduce drug absorption. Oral absorption modeling and simulation for formulation. Absorption enhancing excipients in systemic nasal drug delivery. Mark this risk when a client is taking a drug or medication that can interfere with nutrient intake or use.
Some drugs are irritating and should be administered with meals to reduce adverse effects. Explain how bioavailability can impact drug response and product selection. However, advances in technology over the past decade have allowed alternative methods to be employed to obtain both clinical adme and pharmacokinetic pk. If drugs are absorbed by passive diffusion through a lipoid membrane, their rate. Describe the factors which determine the timecourse of systemic accumulation of a drug administered by infusion or multiple doses. Full text full text is available as a scanned copy of the original print version. 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. Absorption pharmacokinetics an overview sciencedirect. May 07, 2012 the book emphasizes oral absorption, explaining all the physicochemical methods used today to analyze drug candidates. This article has been cited by other articles in pmc. Absorption from either route is rapid, sublingual more so apparently because of greater permeability of sublingual membranes and rich blood supply.
Absorption is used to described the journey of a drug travelling from the site of administration to site of action successfully describing absorption involves several steps. The book emphasizes oral absorption, explaining all the physicochemical methods used. Practical approach to modeling the impact of amorphous. To maintain high concentrations of the drug and additives at the absorption site are possible. Drugs can be absorbed from the oral cavity itself or sublingually. Absorption is the process of delivering a drug into the blood stream. Describe two types of drug interaction and explain how they might affect drug response and safety. Clinical pharmacokinetics is the application of pharmacokinetic principles to the safe and effective therapeutic management of drugs in an individual patient. Basic pharmacokinetics sample chapter pharmaceutical press. Food, other drugs, and digestive disorders can affect drug absorption and bioavailability. The book emphasizes oral absorption, explaining all the physicochemical methods used today to analyze drug candidates. Absorption can be accomplished by administering the drug in a variety of different ways e. Some drugs, notably insulin, are routinely administered sc.
It is also a carrier mediated transport system, differing from active transport in that drug moves along a concentration gradient i. Moreover, the author provides expert guidance to help readers analyze the results of their studies in order to select the most promising drug candidates. Introduction to pharmacokinetics and pharmacodynamics. Explains how to perform and analyze the results of the latest physicochemical methods with this book as their guide, readers have access to all the current information needed to thoroughly investigate and accurately determine a compounds pharmaceutical properties and their effects on drug absorption. Abrahamsson, in comprehensive medicinal chemistry ii, 2007. Drug interactions that affect absorption occur when one drug reduces the bioavailability of a second drug. Overview of factors affecting oral drug absorption naining song a,b, shaoy u zhang b, changxiao liu a a tianjin state key laboratory of pharmacokinetics and pharmaco dynamics, tianjin inst. To maintain high concentrations of the drug and additives at. The main mechanism for the absorption of the drug in to oral mucosa is via passive diffusion into the lipoidal membrane3. It also occurs by subcutaneous, intra muscular and transdermal routes of administration of drugs. This is because the use activity and absorption using univariate property con of a ratio by itself causes a loss of information.