Consider the three barbituric acid derivatives thiopental, secobarbital, and barbital with respective pka of 7. Formulation factors affecting the dissolution rates of drugs from tablets and capsules, and thus influencing their absorption characteristics, include the surface area, polymorphic form, solvates and salt of the drug, the excipients and the process of manufacture. Greater the lipid water solubility coefficient, more is the lipid solubility of the drug and greater is the absorption. For unmarketed drugs that do not have full nda approval by the fda, invitro and or invivo bioequivalence studies must be performed on the drug formulation. The factors affecting absorption of drugs are related both to the drugs and to the body factors related to drugs. If bioavailability from the solid dosage form is lower than that from an oral solution, then. Factors affecting bioavailability global events usa. Drugs which bind selectively to plasma proteins or other blood components ex. The stability of drug in gi tract stomach and intestine also affects the bioavailability of drug. Problem eliminated by evacuating surface from adsorbed air or by use of surfactants. Other approach to enhance the dissolution and absorption rate of certain drugs is by formation of in situ salt formation i. Bioavailability physicochemical and dosage form factors. Such improvements in bioavailability can result in an increased incidence of sideeffects.
Definitions pharmacokinetics oevaluate the way in which a drug interacts with various barriers within a biological system pharmacodynamics ostudy of the relationship between systemic exposure of a drug and its biological effects on tissue oabsorption can be defined as the movement of active drug or prodrug from the site of administration across biologic. Bioavailability of ampicillin and amoxicillin in fasted and nonfasted subjects. The absolute availability of a drug may be determined by comparing the respective area under the. Significance of bioavailability drugs having low therapeutic index, e. Warfarin has v d of about 10litres drugs which bind selectively to extra. Pactf is t he fundamental knowledge base which allows to analyse the factors which influence bioavailability several factors can influence the bioavailability of a drug.
This presentation aims to focus on situations of irregular bioavailability in the case of certain drugs or altered bioavailability in certain situations. May 19, 2012 excipients are generally pharmacologically inert, but can interact with drugs in the dosage form and the physiological factors at the site of absorption to affect the bioavailability of a drug product. Importance of bioavailability in the pharmaceutical world. 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. The influence of total bioavailability on pharmacologic activity obtains whether the drug is given as. Factors affecting bioavailability flashcards quizlet.
Drug bioavailability clinical pharmacology merck manuals. If the drug does not dissolve readily or cannot penetrate the epithelial membrane eg, if it is highly ionized and polar, time at the absorption. The bioavailability of orally administered drugs may be altered by changes in dissolution rate, intestinal microflora, intraluminal enzymes, epithelial enzymes, rate of passage across the gastrointestinal epithelium, gastric emptying rate, intestinal transit time, hepatic first pass. So these drugs invivo exhibit excellent wetting due to presence of natural surfactants such as bile salts. There are many recent advances and factors affecting bioavailability. There is limited documented information on the extent of drug abuse among secondary school students kisumu town east, kenya. Larger the bulk of the meal, longer the gastric time and however an initial rapid rate of emptying is observed with large meal volume and initial lag. Abstract for poorly soluble drugs, the digestive absorption depends on their rate of dissolution. Factors affecting bioavailability and bioequivalence. When the standard consists of intravenously administered drug, this is known.
Director clinical pharmacology program october 1, 2015 office of clinical research training and medical education national institutes of. If absorbance is decreased, bioavailability is decreased and vice versa. Director clinical pharmacology program september 30, 2010 office of clinical research training and medical education national institutes of health clinical center goals of drug absorption and bioavailability lecture factors affecting drug absorption estimation of. If oral drug bioavailability is poor due to metabolism by enzymes in the gastrointestinal tract or in the liver, then a higher dose may be needed, as in the case of propranolol, or an alternative route of drug administration, as in the case of insulin.
In order to identify and analyse the factors which influence bioavailability, all bioavailability results and their associated data have been integrated into one file. The expert system impactf predicts oral bioavailability of novel drugs in humans much more reliable than animal trials. The converse argument, of course, would apply to weakly basic drugs. Jun 22, 2016 if oral drug bioavailability is poor due to metabolism by enzymes in the gastrointestinal tract or in the liver, then a higher dose may be needed, as in the case of propranolol, or an alternative route of drug administration, as in the case of insulin. A mechanistic approach to understanding the factors. Brief introduction to bioavailability objectives of bioavailability methods of assessing bioavailability concept of equivalence references 2.
Pharmaceutic factors affecting drug bioavailability toxicology. In pharmacokinetics, bioavailability is related to 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. This enables userfriendly database queries to receive information about detailed trials on specific diseases, the effect of coadministrated drugs, different drug formulations. Bioavailability means the rate and extent of absorption of the drug from its dosage form bioavailability are very important for any drug for its. Iinnttrroodduuccttiioonn bioavailability is defined as rate and extent of absorption of unchanged drug from its dosage form and become available at. This information is thought to have significant value for school counselors who implement. Factors affecting drug absorption and distribution. Some drugs, such as penicillin g, which is unstable in the acid media of stomach is buffered or enteric coated to protect the drug from degradation at a low ph. Product bioavailability can also be markedly influenced by patient attributes such as the integrity of the gastrointestinal tract, physiological status, site of drug absorption, membrane transporters, presystemic drug metabolism intrinsic variables, and extrinsic variables such as the effect of food or concomitant medication. Drug bioavailability an overview sciencedirect topics. The drugs are chemically indistinguishable in each form the molecules in a metastable crystal are in a higher or lower energy level than those in the stable form of the drug. This is actually the case for many weakly acidic drugs. Physiological factors affecting the dissolution rate of drugs. This article throws light upon the five major factors modifying drug effect and dosage.
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. Pdf overview of factors affecting oral drug absorption. Pharmainformatic is a german biotech company, which provides admetox knowledge bases and predictive tools expert systems to improve drug discovery and development. Pdf this article provides an overview of variables that can affect drug absorption following oral administration in recent years, including both. Fraction of the dose of a drug contained in any dosage form that reaches the systemic circulation in unchanged or active form administered through any route is known as bioavailability. Factors affecting absorption may be classified as those related to the drug and those related to the body. A mechanistic approach to understanding the factors affecting. Most drugs bind to albumin, but some, such as qui 2 determining the percentage oral bioavailability p l a s m a c o n c e n t r a t i o n o f d r u g time % oral bioavailability yx x 100 area under the curve for intravenous drug x area under the curve for oral drug y 3 possible reasons for low oral bioavailability reason drug drug. We would expect their absorption from the stomach to be poor. Factors affecting drug abuse in adolescent females in rural.
Director clinical pharmacology program october 1, 2015 office of clinical research training and medical education national institutes of health clinical center. Most drugs are weak electrolytes the nature and type of salt formation influence drug solubility and bioavailability. Funding and disclosures part one appeared in the august 1 issue. 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. Bioavailability can also be determined for other extravascular routes of administration such as intramuscular, subcutaneous, rectal, mucosal, sublingual, transdermal etc. For instance, the diffusion coefficient, d, of the drug in the gastrointestinal fluids may be decreased by the presence of substances that increase the viscosity of the fluids.
Iinnttrroodduuccttiioonn bioavailability is defined as rate and extent of absorption of unchanged drug from its dosage form and become available at the site of action. The various factors affecting bioavailability of drugs can be classified as shown in. Bioavailability is affected by factors that influence absorption. Pharmaceutic factors affecting drug bioavailability. Drug absorption drugs merck manuals consumer version. As presviously described, approximately 40% of the existing. The effects of drugs part i a s noted in chapter 1, the use of substances for their consciousnessaltering effects is ubiquitous in human history. Warfarin have apparent volume of distribution smaller than true volume of distribution. In pharmacology, relative bioavailability measures the bioavailability estimated as the auc of a formulation a of a certain drug when compared with another formulation b of the same drug, usually an established standard, or through administration via a different route. Bioavailability and factors affecting bioavailability simple. The term outright bioavailability is utilized when the portion of retained medication is identified with its i.
Due to their generally good systemic availability, solutions are frequently used as bioavailability standards against which other dosage forms are compared. For example, highfiber foods and calcium supplements may bind with a drug and prevent it from being absorbed. Food, other drugs, and digestive disorders can affect drug absorption and bioavailability. Factors modifying drug effect and dosage pharmacodynamics. Factors affecting absorption of a drug from its dosage form.
Hence, the metastable form has a higher or lower melting point and a higher or lower solubility and dissolution rates. Laxatives and diarrhea, which speed up the passage of substances through the digestive tract, may reduce drug absorption. Absolute dose of a drug varies with species as different species are of different sizes. Excipients are generally pharmacologically inert, but can interact with drugs in the dosage form and the physiological factors at the site of absorption to affect the bioavailability of a drug product. Low bioavailability is most common with oral dosage forms of poorly watersoluble, slowly absorbed drugs.
Effect of level of first pass metabolism of drug on its bioavailability. Impact of excipient interactions on drug bioavailability. Impact of excipient interactions on drug bioavailability from. Bioavailability of most small molecular weight drugs administered i. The term relative bioavailability is utilized to look at two changed extravascular courses of medication organization 14 18. Factors affecting bioavailability learn with flashcards, games, and more for free. These include drug formulation, coadministration of another drug, feeding condition, the age and gender of the subjects involved, dosing scheme, genetic differences and specific. This paper focuses on drugexcipient interactions in solid dosage forms that.
The bioavailability of orally administered drugs may be altered by changes in dissolution rate, intestinal microflora, intraluminal enzymes, epithelial enzymes, rate of passage across the gastrointestinal epithelium, gastric emptying rate, intestinal transit time, hepatic first pass metabolism, and gastrointestinal and hepatic blood flow. The environment of the gastrointestinal tract can affect the parameters of the noyeswhitney equation and hence the dissolution rate of a drug. Bioavailability means the rate and extent to which the active ingredient is absorbed from a drug product and becomes available at the site of. Factors affecting drug bioavailability in space tietze. Sublingual and rectal routes are often used to bypass hepatic firstpass effect. Factors affecting cadmium bioavailability sludge characteristics data from laboratory, greenhouse, and field all show that sludge characteristics are extremely important, if not dominant, in controlling cd and zn availability to plants. From 18% to 63% of the total zn, and from 12% to 63% of the total cd in the sewage sludges studied was. For unmarketed drugs that do not have full nda approval by the fda, invitro andor invivo bioequivalence studies must be performed on the drug formulation. Factors affecting bioactivity how drugs act drug times.
A general mechanistic understanding of the basis of these interactions is essential to design robust drug products. Decreasing the particle size of these drugs improves their rate of dissolution. Insufficient time for absorption in the gi tract is a common cause of low bioavailability. Examples of drugs where a reduction in particle size has been shown to improve the rate and extent of oral absorption and hence bioavailability are shown in table 20. Factors effecting bioavailability studies the pharma innovation. There is evidence that psychoactive plants such as ephedra were used by neanderthal man as far back as 50,000 years ago merlin, 2003, and all civilizations that have had access to these. Factors influencing bioavailability pharmainformatic.
The influence of the dosage form on the bioavailability of. Drugs injected using intravenous route of administration have 100% bioavailability, while others have much less bioavailability, because. For a drug to be readily absorbed, it must be hydrophobic yet have some solubility in aqueous solution 3. Factors influencing bioavailability of drugs pdf free download as pdf file. Bioavailability is less or equivalent to 100% for some other course of organization. Product bioavailability can also be markedly influenced by patient attributes such as the integrity of the gastrointestinal tract, physiological status, site of drug absorption, membrane transporters, presystemic drug metabolism intrinsic variables, and extrinsic variables such as. The main objective of this study was to investigate environmental and demographic factors influencing drug and substance abuse among secondary school students in kisumu town east, kenya. Lipid water solubility coefficient is the ratio of dissolution of drug in lipid as compared to water.
Drugs may also be formulated in the soft gelatin capsule to reduce gi irritation. Factors affecting drug abuse in adolescent females in. The influence of the dosage form on the bioavailability of drugs. Hydrophobic drugs like phenacetin, aspirin shows decrease in dissoln rate as they tend to adsorb air at the surface and inhibit their wettability. It includes absorption, metabolism and food effect of drugs. The v d of such drugs lies between blood volume and tbw volume. Factors affecting drug bioavailability in space american college of.
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