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Bioavailability

From Wikipedia, the free encyclopedia

In  pharmacology, bioavailability (BA) is a subcategory of absorption and is the fraction of anadministered dose of unchanged drug that reaches the systemic circulation, one of the principal

 pharmacokinetic  properties of  drugs. By definition, when a medication is administered

intravenously, its bioavailability is 100%.[1]

 However, when a medication is administered via otherroutes (such as orally), its bioavailability generally

TH[›] decreases (due to incomplete absorption and

first-pass metabolism) or may vary from patient to patient. Bioavailability is one of the essential

tools in pharmacokinetics, as bioavailability must be considered when calculating dosages for non-intravenous routes of administration.

For  dietary supplements, herbs and other nutrients in which the route of administration is nearlyalways oral, bioavailability generally designates simply the quantity or fraction of the ingested dose

that is absorbed.

[2]

 

Bioavailability is defined slightly differently for drugs as opposed to dietary supplements 

 primarily due to the method of administration and Food and Drug Administration regulations.

Bioaccessibility is a concept related to bioavailability in the context of   biodegradation and

environmental pollution. A molecule (often a  persistent organic pollutant) is said to be bioavailable

when "[it] is available to cross an organism’s cellular membrane  from the environment, if theorganism has access to the chemical." 

[3] 

Contents

  1 Definitions 

o  1.1 In pharmacology 

o  1.2 In nutritional sciences 

o  1.3 In environmental sciences 

  2 Absolute bioavailability 

  3 Relative bioavailability and bioequivalence 

  4 Factors influencing bioavailability 

  5 Bioavailability of drugs versus dietary supplements 

  6 Nutritional science: reliable and universal bioavailability 

  7 See also 

 

8 Notes   9 References 

  10 Sources 

  11 External links 

Definitions

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In pharmacology

In pharmacology, bioavailability is a measurement of the rate and extent to which a drug reaches

the systemic circulation.[4]

 It is denoted by the letter f  (or, if expressed in percent, by F ).

In nutritional sciences

In nutritional sciences, which covers the intake of nutrients and non-drug dietary ingredients, the

concept of bioavailability lacks the well-defined standards associated with the pharmaceutical

industry. The pharmacological definition cannot apply to these substances because utilization andabsorption is a function of the nutritional status and physiological state of the subject,

[5] resulting in

even greater differences from individual to individual (inter-individual variation). Therefore,

 bioavailability for dietary supplements can be defined as the proportion of the administered

substance capable of being absorbed and available for use or storage.[6]

 

In both pharmacology and nutrition sciences, bioavailability is measured by calculating the area

under curve (AUC) of the drug concentration time profile.

In environmental sciences

Bioavailability is commonly a limiting factor in the production of crops (due to solubility

limitation or adsorption of plant nutrients to soil colloids) and in the removal of toxic substances

from the food chain by microorganisms (due to sorption to or partitioning of otherwise degradablesubstances into inaccessible phases in the environment). A noteworthy example for agriculture is

 plant phosphorus deficiency induced by precipitation with iron and aluminum phosphates at low soil

 pH and precipitation with calcium phosphates at high soil pH.[7]

 Toxic materials in soil, such as lead

from paint may be rendered unavailable to animals ingesting contaminated soil by supplying

 phosphorus fertilizers in excess.[8]

 Organic pollutants such as solvents or pesticides[9]

 may berendered unavailable to microorganisms and thus persist in the environment when they are adsorbed

to soil minerals[10]

 or partition into hydrophobic organic matter .[11]

 

Absolute bioavailability

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Absolute bioavailability is a ratio of areas under the curves. IV, intravenous; PO, oral route.

Absolute bioavailability compares the bioavailability of the active drug in systemic circulationfollowing non-intravenous administration (i.e., after  oral, rectal, transdermal, subcutaneous, or

sublingual administration), with the bioavailability of the same drug following intravenous

administration. It is the fraction of the drug absorbed through non-intravenous administrationcompared with the corresponding intravenous administration of the same drug. The comparison must

 be dose normalized (e.g., account for different doses or varying weights of the subjects);

consequently, the amount absorbed is corrected by dividing the corresponding dose administered.

In pharmacology, in order to determine absolute bioavailability of a drug, a  pharmacokinetic 

study must be done to obtain a plasma drug concentration vs time plot for the drug after bothintravenous (iv) and extravascular (non-intravenous, i.e., oral) administration. The absolute

 bioavailability is the dose-corrected area under curve (AUC) non-intravenous divided by AUC

intravenous. For example, the formula for calculating F  for a drug administered by the oral route

(po) is given below.

Therefore, a drug given by the intravenous route will have an absolute bioavailability of 100%( f =1), whereas drugs given by other routes usually have an absolute bioavailability of less than one.

If we compare the two different dosage forms having same active ingredients and compare the two

drug bioavailability is called comparative bioavailability.

Although knowing the true extent of systemic absorption (referred to as absolute bioavailability)

is clearly useful, in practice it is not determined as frequently as one may think. The reason for this is

that its assessment requires an intravenous reference, that is, a route of administration that guaranteesthat all of the administered drug reaches the systemic circulation. Such studies come at considerable

cost, not least of which is the necessity to conduct preclinical toxicity tests to ensure adequate safety,as well as there being potential problems due to solubility limitations. These limitations may be

overcome, however, by administering a very low dose (typically a few micrograms) of an

isotopically labelled drug concomitantly with a therapeutic non-labelled oral dose. Providing theisotopically-labelled intravenous dose is sufficiently low so as not to perturb the systemic drug

concentrations achieved from the absorbed oral dose, then the intravenous and oral pharmacokinetics

can be deconvoluted by virtue of the their different isotopic constitution and thereby determine the

oral and intravenous pharmacokinetics from the same dose administration. This technique eliminates pharmacokinetic issues on non-equivalent clearance as well as enabling the intravenous dose to be

administered with a minimum of toxicology and formulation. The technique was first applied usingstable-isotopes such as C-13 and mass-spectrometry to distinguish the isotopes by mass difference.More recently, C-14 labelled drugs are administered intravenously and accelerator mass

spectrometry (AMS) used to measure the isotopically labelled drug along with mass spectrometry

for the unlabelled drug.[12]

 

There is no regulatory requirement to define the intravenous pharmacokinetics or absolute

 bioavailability however regulatory authorities do sometimes ask for absolute bioavailability

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information of the extravascular route in cases in which the bioavailability is apparently low or

variable and there is a proven relationship between the  pharmacodynamics and the pharmacokinetics

at therapeutic doses. In all such cases, to conduct an absolute bioavailability study requires that thedrug be given intravenously.

[13] 

Intravenous administration of a developmental drug can provide valuable information on thefundamental pharmacokinetic parameters of  volume of distribution (V) and clearance (CL).[13]

 

Relative bioavailability and bioequivalence

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. When the standardconsists of intravenously administered drug, this is known as absolute bioavailability (see above).

Relative bioavailability is one of the measures used to assess  bioequivalence (BE) between two

drug products. For FDA approval, a generic manufacturer must demonstrate that the 90% confidence

interval for the ratio of the mean responses (usually of AUC and the maximum concentration, Cmax)of its product to that of the "Brand Name drug"

OB[›] is within the limits of 80% to 125%. While AUC

refers to the extent of bioavailability, Cmax refers to the rate of bioavailability. When Tmax is given, it

refers to the time it takes for a drug to reach Cmax.

While the mechanisms by which a formulation affects bioavailability and bioequivalence have

 been extensively studied in drugs, formulation factors that influence bioavailability and

 bioequivalence in nutritional supplements are largely unknown.[14] As a result, in nutritionalsciences, relative bioavailability or bioequivalence is the most common measure of bioavailability,

comparing the bioavailability of one formulation of the same dietary ingredient to another.

Factors influencing bioavailability

The absolute bioavailability of a drug, when administered by an extravascular route, is usuallyless than one (i.e., F  <100%). Various physiological factors reduce the availability of drugs prior to

their entry into the systemic circulation. Whether a drug is taken with or without food will also affect

absorption, other drugs taken concurrently may alter absorption and first-pass metabolism, intestinal

motility alters the dissolution of the drug and may affect the degree of chemical degradation of thedrug by intestinal microflora. Disease states affecting liver metabolism or gastrointestinal function

will also have an effect.

Other factors may include, but are not limited to:

  Physical properties of the drug (hydrophobicity,  pKa, solubility) 

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  The drug formulation (immediate release, excipients used, manufacturing methods,

modified release  –  delayed release, extended release, sustained release, etc.)

  Whether the formulation is administered in a fed or  fasted state

  Gastric emptying rate

  Circadian differences

 

Interactions with other drugs/foods:o  Interactions with other drugs (e.g., antacids, alcohol, nicotine)

o  Interactions with other foods (e.g., grapefruit juice,  pomello, cranberry juice, 

 brassica vegetables)

  Transporters: Substrate of  efflux transporters (e.g. P-glycoprotein) 

  Health of the GI tract 

  Enzyme induction/inhibition by other drugs/foods:

o  Enzyme induction (increased rate of metabolism), e.g., Phenytoin induces

CYP1A2, CYP2C9, CYP2C19, and CYP3A4 

o  Enzyme inhibition (decreased rate of metabolism), e.g., grapefruit juice inhibits

CYP3A → higher nifedipine concentrations 

 

Individual variation in metabolic differenceso  Age: In general, drugs are metabolized more slowly in fetal, neonatal, and

geriatric populations

o  Phenotypic differences, enterohepatic circulation, diet, gender

  Disease state

o  E.g., hepatic insufficiency, poor  renal function

Each of these factors may vary from patient to patient (inter-individual variation), and indeed in

the same patient over time (intra-individual variation). In clinical trials, inter-individual variation is a

critical measurement used to assess the bioavailability differences from patient to patient in order to

ensure predictable dosing.

Bioavailability of drugs versus dietary supplements

In comparison to drugs, there are significant differences in dietary supplements that impact the

evaluation of their bioavailability. These differences include the following: the fact that nutritional

supplements provide benefits that are variable and often qualitative in nature; the measurement of

nutrient absorption lacks the precision; nutritional supplements are consumed for prevention andwell-being; nutritional supplements do not exhibit characteristic dose-response curves; and dosing

intervals of nutritional supplements, therefore, are not critical in contrast to drug therapy.[6]

 

In addition, the lack of defined methodology and regulations surrounding the consumption of

dietary supplements hinders the application of bioavailability measures in comparison to drugs. Inclinical trials with dietary supplements, bioavailability primarily focuses on statistical descriptions ofmean or average AUC differences between treatment groups, while often failing to compare or

discuss their standard deviations or inter-individual variation. This failure leaves open the question

of whether or not an individual in a group is likely to experience the benefits described by the mean-difference comparisons. Further, even if this issue were discussed, it would be difficult to

communicate meaning of these inter-subject variances to consumers and/or their physicians.

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Nutritional science: reliable and universal bioavailability

One way to resolve this problem is to define "reliable bioavailability" as positive bioavailability

results (an absorption meeting a predefined criteria) that include 84% of the trial subjects and"universal bioavailability" as those that include 98% of the trial subjects. This reliable-universal

framework would improve communications with physicians and consumers such that, if it wereincluded on products labels for example, make educated choices as to the benefits of a formulationfor them directly. In addition, the reliable-universal framework is similar to the construction of

confidence intervals, which statisticians have long offered as one potential solution for dealing with

small samples, violations of statistical assumptions or large standard deviations.[15]

 

See also

  ADME-Tox 

  Lipinski's Rule of 5 

 

Biopharmaceutics Classification System   Caco-2 

Notes

^ TH: One of the few exceptions where a drug shows F  of >100% is theophylline. Ifadministered as an oral solution F  is 111%, since the drug is completely absorbed and first-past

metabolism in the lung after iv administration is bypassed.[16]

 

^ OB: Reference listed drug products (i.e., innovator's) as well as generic drug products that have

 been approved based on an Abbreviated New Drug Application are given in FDA's "Orange Book ".

References

1.  Griffin, J.P. The Textbook of Pharmaceutical Medicine (6th Ed.). New Jersey:

BMJ Books. ISBN 978-1-4051-8035-1[ page needed ]

 

2.  Heaney, Robert P. (2001). "Factors Influencing the Measurement ofBioavailability, Taking Calcium as a Model". The Journal of Nutrition 131 (4): 1344S – 8S.

PMID 11285351. 

3.  Semple, Kirk. T.; Doick, Kieron J.; Jones, Kevin C.; Burauel, Peter; Craven,

Andrew; Harms, Hauke (2004). "Peer Reviewed: Defining Bioavailability and Bioaccessibility ofContaminated Soil and Sediment is Complicated". Environmental Science & Technology 38 (12):

228A – 31A. doi:10.1021/es040548w. 

4. 

Shargel, L.; Yu, A.B. (1999). Applied biopharmaceutics & pharmacokinetics (4th

ed.). New York: McGraw-Hill. ISBN 0-8385-0278-4[ page needed ]

 5.  Heaney, Robert P. (2001). "Factors Influencing the Measurement of

Bioavailability, Taking Calcium as a Model". The Journal of Nutrition 131 (4 Suppl): 1344S – 8S.

PMID 11285351. 

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6.  Srinivasan, V. Srini (2001). "Bioavailability of Nutrients: A Practical Approach to

In Vitro Demonstration of the Availability of Nutrients in Multivitamin-Mineral Combination

Products". The Journal of Nutrition 131 (4 Suppl): 1349S – 50S. PMID 11285352. 7.  Hinsinger, Philippe (2001). "Bioavailability of soil inorganic P in the rhizosphere

as affected by root-induced chemical changes: a review". Plant and Soil  237 (2): 173 – 95.

doi:10.1023/A:1013351617532. 8.  Ma, Qi Ying; Traina, Samuel J.; Logan, Terry J.; Ryan, James A. (1993). "In situlead immobilization by apatite". Environmental Science & Technology 27 (9): 1803 – 10.

doi:10.1021/es00046a007. 

9.  Sims, G.K.; M. Radosevich, X.T. He, and S.J. Traina. (1991). "The effects ofsorption on the bioavailability of pesticides". In W. B. Betts (ed.). Biodegradation of natural and

 synthetic materials. Springer Verlag, London: 119 – 137.

10.  O'Loughlin, Edward J.; Traina, Samuel J.; Sims, Gerald K. (2000). "Effects of

sorption on the biodegradation of 2-methylpyridine in aqueous suspensions of reference clayminerals". Environmental Toxicology and Chemistry 19 (9): 2168 – 74. doi:10.1002/etc.5620190904. 

11.  Sims, Gerald K; Cupples, Alison M (1999). "Factors controlling degradation of

 pesticides in soil". Pesticide Science 55 (5): 598 – 601. doi:10.1002/(SICI)1096-9063(199905)55:5<598::AID-PS962>3.0.CO;2-N. 

12.  Lappin, Graham; Rowland, Malcolm; Garner, R Colin (2006). "The use of

isotopes in the determination of absolute bioavailability of drugs in humans". Expert Opinion on

 Drug Metabolism & Toxicology 2 (3): 419 – 27. doi:10.1517/17425255.2.3.419. PMID 16863443. 13.  Lappin, Graham; Stevens, Lloyd (2008). "Biomedical accelerator mass

spectrometry: Recent applications in metabolism and pharmacokinetics". Expert Opinion on Drug

 Metabolism & Toxicology 4 (8): 1021 – 33. doi:10.1517/17425255.4.8.1021. PMID 18680438. 14.  Hoag, Stephen W.; Hussain, Ajaz S. (2001). "The Impact of Formulation on

Bioavailability: Summary of Workshop Discussion". The Journal of Nutrition 131 (4 Suppl):

1389S – 91S. PMID 11285360. 

15.  Kagan, Daniel; Madhavi, Doddabele; Bank, Ginny; Lachlan, Kenneth (2010)."'Universal' and 'Reliable' Bioavailability Claims: Criteria That May Increase Physician Confidence

in Nutritional Supplements".  Natural Medicine Journal  2 (1): 1 – 5.

16.  Schuppan, D; Molz, KH; Staib, AH; Rietbrock, N (1981). "Bioavailability oftheophylline from a sustained-release aminophylline formulation (Euphyllin retard tablets)--plasma

levels after single and multiple oral doses". International journal of clinical pharmacology, therapy,

and toxicology 19 (5): 223 – 7. PMID 7251238. 

Sources

  Malcolm Rowland; Thomas N. Tozer (2010). Clinical Pharmacokinetics and

 Pharmacodynamics: Concepts and Applications (4 ed.). Philadelphia, PA: Lippincott Williams &Wilkins. ISBN 978-0-7817-5009-7. 

  Peter G. Welling; Francis L. S. Tse; Shrikant V. Dighe (1991). Pharmaceutical

 Bioequivalence. Drugs and the Pharmaceutical Sciences 48. New York, NY: Marcel Dekker.ISBN 978-0-8247-8484-3. 

  Dieter Hauschke; Volker Steinijans; Iris Pigeot (2007). "Metrics to characterize

concentration-time profiles in single- and multiple-dose bioequivalence studies".  Bioequivalence

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Studies in Drug Development: Methods and Applications. Statistics in Practice. Chichester, UK:

John Wiley and Sons. pp. 17 – 36. ISBN 978-0-470-09475-4. Retrieved 21 April 2011.

  Shein-Chung Chow; Jen-pei Liu (15 October 2008). Design and Analysis of

 Bioavailability and Bioequivalence Studies. Biostatistics Series 27 (3 ed.). Boca Raton, FL: CRC

Press. ISBN 978-1-58488-668-6. 

BIOAVAILABILITY

Definition : "Fraction of a dose of drug that is absorbed from its site of administration and

reaches, in an unchanged form, the systemic circulation."

Description

The drug, its route of administration and its galenic formulation determine the amount of

administered dose absorbed into the circulation. Patient dependant factors also influence

 bioavailability.

When the drug is administered orally the bioavailability depends on several factors:

1.  Physicochemical properties of the drug and its excipients that determine its dissolution inthe intestinal lumen and its absorption across the intestinal wall.

2.  Decomposition of the drug in the lumen.

3.   pH and perfusion of the small intestine.

4.  Surface and time available for absorption.5.  Competing reactions in the lumen (for example of the drug with food).

6.  Hepatic first-pass effect. 

Bioavailability can also be determined for other  extravascular  routes of administration such as

intramuscular, subcutaneous, rectal, mucosal, sublingual, transdermal etc. Sublingual and rectal

routes are often used to bypass hepatic first-pass effect. Bioavailability of most small molecularweight drugs administered i.m. or s.c. are perfusion rate-limited. Large molecules administered i.m

or s.c. enter the blood in part via the lymphatic pathway.

Clinical implications

When changing the route of administration or the formulation of a drug, the dose must be

adapted with regard to the respective bioavailability of each route.

Related terms

Bioavailability of a drug administered intravenously is by definition 100%. Bioavailability is less

or equal to 100% for any other route of administration.

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The term absolute bioavailability is used when the fraction of  absorbed drug is related to its i.v.

 bioavailability. The term relative bioavailability is used to compare two different extravascular  

routes of drug administration.

The term bioequivalence is used when two different galenic formulations of a drug have a

similar bioavailability.

Assessment

Bioavailability is proportional to the total area under the plasma concentration-time curve 

(AUC). The relative bioavailability of drug 1 compared to drug 2 can be calculated using the

following equation:

Bioequivalence

From Wikipedia, the free encyclopedia

A bioequivalency profile comparison of 150 mg extended-release  bupropion as produced byImpax Laboratories for  Teva and Biovail for  GlaxoSmithKline. 

Bioequivalence is a term in  pharmacokinetics used to assess the expected in vivo  biologicalequivalence of two proprietary preparations of a drug. If two products are said to be bioequivalent it

means that they would be expected to be, for all intents and purposes, the same.

Birkett (2003) defined bioequivalence by stating that, "two pharmaceutical products are

 bioequivalent if they are pharmaceutically equivalent and their   bioavailabilities (rate and extent of

availability) after administration in the same molar dose are similar to such a degree that theireffects, with respect to both efficacy and safety, can be expected to be essentially the same.

Pharmaceutical equivalence implies the same amount of the same active substance(s), in the same

dosage form, for the same route of administration and meeting the same or comparable standards."[1]

 

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The United States Food and Drug Administration (FDA) has defined bioequivalence as, "the

absence of a significant difference in the rate and extent to which the active ingredient or active

moiety in pharmaceutical equivalents or pharmaceutical alternatives becomes available at the site ofdrug action when administered at the same molar dose under similar conditions in an appropriately

designed study."[2]

 

Contents

  1 Bioequivalence 

  2 Regulatory definition 

o  2.1 Australia 

o  2.2 Europe 

o  2.3 United States 

  3 See also 

  4 References 

  5 Further reading 

Bioequivalence

In determining bioequivalence, for example, between two products such as a commercially-available Brand product and a potential to-be-marketed Generic product, pharmacokinetic studies areconducted whereby each of the preparations are administered in a cross-over study to volunteer

subjects, generally healthy individuals but occasionally in patients. Serum/plasma samples are

obtained at regular intervals and assayed for parent drug (or occasionally metabolite) concentration.Occasionally, blood concentration levels are neither feasible or possible to compare the two products

(e.g. inhaled corticosteroids), then pharmacodynamic endpoints rather than pharmacokinetic

endpoints (see below) are used for comparison. For a pharmacokinetic comparison, the plasmaconcentration data are used to assess key pharmacokinetic parameters such as area under the curve(AUC), peak concentration (Cmax), time to peak concentration (Tmax), and absorption lag time (tlag).

Testing should be conducted at several different doses, especially when the drug displays non-linear

 pharmacokinetics.

In addition to data from bioequivalence studies, other data may need to be submitted to meetregulatory requirements for bioequivalence. Such evidence may include:

  analytical method validation

  in vitro-in vivo correlation studies(IVIVC)

Regulatory definition

Australia

In Australia, the Therapeutics Goods Administration (TGA) considers preparations to be

 bioequivalent if the 90% confidence intervals (90% CI) of the rate ratios, between the two

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 preparations, of Cmax and AUC lie in the range 0.80-1.25. Tmax should also be similar between the

 products.[1]

 

There are tighter requirements for drugs with a narrow therapeutic index and/or saturable

metabolism –  thus no generic products exist on the Australian market for  digoxin or   phenytoin for

instance.

Europe

According to regulations applicable in the European Economic Area[3]

 two medicinal products

are bioequivalent if they are pharmaceutically equivalent or pharmaceutical alternatives and if their

 bioavailabilities after administration in the same molar dose are similar to such a degree that their

effects, with respect to both efficacy and safety, will be essentially the same. This is considereddemonstrated if the 90% confidence intervals (90% CI) of the ratios for AUC0-t and Cmax between the

two preparations lie in the range 80.00 –  125.00%.

United States

The FDA considers two products bioequivalent if the 90% CI of the relative mean Cmax, AUC(0-t) 

and AUC(0-∞) of the test (e.g. generic formulation) to reference (e.g. innovator brand formulation)should be within 80.00% to 125.00% in the fasting state. Although there are a few exceptions,

generally a bioequivalent comparison of Test to Reference formulations also requires administration

after an appropriate meal at a specified time before taking the drug, a so-called "fed" or "food-effect"study. A food-effect study requires the same statistical evaluation as the fasting study, described

above.[2]

 

See also

  Generic drug 

  Pharmacokinetics 

  Clinical trial 

References

1.  Birkett DJ (2003). "Generics - equal or not?".  Aust Prescr  26: 85 – 7.

2.  Center for Drug Evaluation and Research (2003). "Guidance for Industry:

Bioavailability and Bioequivalence Studies for Orally Administered Drug Products —  General

Considerations". United States Food and Drug Administration.3.  Committee for Medicinal Products for Huma

Bioequivalence and

terchangeability of Generic

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rugs

inS

 

When a company develops a generic version of a trade-name drug, the company's experts in

formulation must figure out how to make it. It is not enough for them to simply reproduce

trade-name drug's chemical structure or to buy the active ingredient from a chemical

ufacturer. Although 250 milligrams (mg) of a trade-name chemical is identical to 250 mg ofsame generic chemical, a 250-mg generic pill containing that chemical may or may not have

same effect in the body as a 250-mg trade-name pill. That is because everything that is used

 particular product formulation affects how it is absorbed into the bloodstream. Inactiveedients such as coatings, stabilizers, fillers, binders, flavorings, diluents, and others are

ssary to turn a chemical into a usable drug product. These ingredients may be used to

ide bulk so that a tablet is large enough to handle, to keep a tablet from crumbling betweentime it is manufactured and the time it is used, to help a tablet dissolve in the stomach or

stine, or to provide a pleasant taste and color. Inactive ingredients are usually harmless

tances that do not affect the body. However, because inactive ingredients can cause unusual

sometimes severe allergic reactions in a few people, one version, or brand, of a drug may beerable to another. For example, chemicals called bisulfites (such as sodium metabisulfite),

ch are used as preservatives in many products, cause asthmatic allergic reactions in many

le. Consequently, drug products containing bisulfites are prominently labeled as such.

Bioequivalence:

Manufacturers must conduct studies to determine whether their version is bioequivalent tooriginal drug — that is, that the generic version releases its active ingredient (the drug) into

 bloodstream at virtually the same speed and in virtually the same amounts as the original. Because the active ingredient in the generic drug has already been shown in testing of the

e-name drug to be safe and effective, bioequivalence studies only have to show that the

eric version produces virtually the same levels of drug in the blood over time and thusire only a relatively small number (24 to 36) of healthy volunteers.

Although people generally think of oral dosage forms, such as tablets, capsules, and liquids,n they think about generic prescription drugs, generic versions of other drug dosage forms,

as injections, patches, inhalers, and others, must also meet a bioequivalence standard. The

sets bioequivalence standards for different drug dosage forms.

The manufacturer of the trade-name drug also must prove bioequivalence before a new form

n approved drug can be sold. New forms include new dosage forms or strengths of anting trade-name drug product and any other modified form that is developed, as well as new

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eric drugs. Sometimes the form that was originally tested is modified for commercialons. For example, tablets may need to be made sturdier, flavoring or coloring may be added

hanged, or inactive ingredients may be changed to increase consumer acceptance.

Evaluation and Approval Procedures:

The FDA evaluates every generic version of a drug. The FDA approves a generic drug ifies indicate that the original trade-name drug and the generic version are essentiallyquivalent. The FDA also makes sure that a new generic drug contains the appropriate

unt of the active (drug) ingredient, that it is manufactured according to federal standards

od Manufacturing Practices), and that the generic version differs from its trade-name

terpart in size, color, and shape — a legal requirement.

Interchangeability and Substitution:

Theoretically, any generic drug that is bioequivalent to its trade-name counterpart may berchanged with it. For drugs that are off-patent, the generic drug may be the only form

lable. To limit costs, many doctors write prescriptions for generic drugs whenever possible.n if the doctor has prescribed a trade-name drug, the pharmacist may dispense a generic

unless the doctor wrote on the prescription that no substitution can be made. Also,

rance plans and managed care organizations may require that generic drugs be prescribeddispensed whenever possible to save money. Some plans may allow a consumer to select a

e expensive trade-name product prescribed by the doctor as long as the consumer pays the

erence in cost. However, in some state-run programs, the consumer has no say. If the doctor

cribes a generic drug, the pharmacist must dispense a generic drug. In most states, thesumer may insist on a trade-name drug even if the doctor and pharmacist recommend a

eric drug.

Sometimes generic substitution may not be appropriate. For example, some available

eric versions may not be bioequivalent to the trade-name drug. Such generic drugs may still

sed, but they may not be substituted for the trade-name product. In cases in which smallerences in the amount of drug in the bloodstream can make a very large difference in the

's effectiveness, generic drugs are often not substituted for trade-name drugs, although

quivalent generic products are available. Warfarin

anticoagulant, and phenytoin

anticonvulsant, are examples of such drugs. Finally, a generic product may not beopriate if it contains an inactive ingredient that the person is allergic to. Thus, if a doctor

ifies a trade-name drug on the prescription and the consumer wants an equivalent generic

ion, the consumer or pharmacist should discuss the matter with the doctor.

Drugs that must be given in very precise amounts are less likely to be interchangeable,

use the difference between an effective dose and a harmful or an ineffective dose (thegin of safety) is small. Digoxin

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 d to treat people with heart failure, is an example. Switching from the trade-name version

igoxin

generic product may cause problems, because the two versions may not be sufficiently

quivalent. However, some generic versions of digoxin

e been certified as bioequivalent by the FDA. Pharmacists and doctors can answer questions

t which generic drugs are interchangeable for their trade-name counterparts and which are

A book published by the FDA each year and updated periodically also provides guidance

t which drugs are interchangeable. This book, Approved Drug Products With Therapeuticivalence Evaluations (also known as "the orange book" because it has a bright orange

er), is available both in print and online to anyone but is intended for use by doctors and

macists. See Approved Drug Products With Therapeutic Equivalence Evaluations. 

The substitution of a generic drug can sometimes cause other problems for the consumer. A

or may write a prescription for a trade-name product and discuss the trade-name productthe consumer. If a pharmacist dispenses an equivalent generic product and the label does

also list the reference (trade-name product), the consumer may not know how the generic

uct relates to the drug the doctor prescribed. To prevent this confusion, pharmacists shouldude the reference trade name on the label when a generic product is substituted.

Journal of Bioequivalence & Bioavailability

About the Journal

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Bioequivalence refers to a statistically equal extent and rate of absorption of two

s when administrated at the same molar dose whereas Bioavailability is the rate at

ch the drug appears in the systemic circulation In Vivo. The Journal ofequivalence & Bioavailability provides continuously growing literature and

arch activities on the regulatory requirements, scientific and practical issues, and

stical methodology of the design and analysis of bioequivalence andvailability studies.Journal of Bioequivalence & Bioavailability, an academic journal encompasses a

e range of current research disciplines under the scope of the journal which aims

ffer a promising platform for the authors to make their valuable contributionsards the journal. In Omics publishing group, the editorial office is dedicated to

re the peer review process of the manuscripts by the eminent editors and the

ewers to raise the quality of publishing.

Journal of Bioequivalence & Bioavailability is among the  best open accessnals of the Omics group, set out to publish the most comprehensive, relevant and

 ble information based on the current research and development in the field of

equivalence and Bioavailability. This information can be published in our   peerewed journal with impact factors as original articles, review articles, case reports,

t communications, etc. in the journal which is freely available without any

ictions or any other subscriptions for researchers all over the world with the sole

ntion directed towards the advancement of the scientific world resulting in theerment of the society.

act Factor: 3.08

dex Copernicus V

The journal is maintaining quality by using Editorial Manager System for the review process. Editorial M

nline manuscript submission, review and tracking system. Peer review  process is carried out by our dignorial board members of Bioequivalence & Bioavailability or outside experts. To publish any articles, at l

 pendent reviewer’s approval followed by the editor’s approval is required. Authors may submit manuscr

 their progress through the system, hopefully to publication. Reviewers have the facility to download th

uscripts and submit their suggestions to the editor. Editors can manage the wholeission/review/revise/publish process.