Chiaramente, ogni formato ha i propri vantaggi e svantaggi acquista antibiotici online per effettuare un acquisto, non è necessario fornire la prescrizione medica.
is used to describe the fraction of an administered
reaches the , one of the principal . By definition, when a
medication is administered  However, when a medication is administered
(such as orally), its bioavailability decreases (due to incomplete absorption and
) or may vary from patient to patient (due to inter-individual variation). Bioavailability is one of the
non-intravenous routes of administration.
bioavailability generally designates simply the quantity or fraction of the ingested dose that is absorbed.
method of administration and regulations.
A (often a "[it] is available to cross an
organism's from the environment, if the organism has access to the chemical."
In pharmacology, bioavailability is a measurement of the extent to which a drug reaches the systemic circulation.
It is denoted by the letter 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 and absorption is a function of the nutritional status
and physiological state of the subject, resulting in even greater differences from individual to individual
(inter-individual variation). Therefore, bioavailability for dietary supplements can be defined as the proportion of a
the substance capable of being absorbed and available for use or storage.
In both pharmacology and nutrition sciences, the bioavailability is measured by calculating the , or
AUC, of the drug concentration time profile.
Absolute bioavailability compares the bioavailability of the active drug in systemic circulation following
the bioavailability of the same drug following intravenous administration. It is the fraction of the drug absorbed
through non-intravenous administration compared 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.
obtain a plasma drug concentration vs time
plot for the drug after both intravenous (IV) and non-intravenous
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
Therefore, a drug given by the intravenous route will have an absolute bioavailability of 1 (F=1) while 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 guarantees that 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.
There is no regulatory requirement to define the intravenous pharmacokinetics or absolute bioavailability however
regulatory authorities do sometimes ask for absolute bioavailbility 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 the drug be given intravenously.
Intravenous administration of a developmental drug can provide valuable information on the fundamental
pharmacokinetic parameters of volume of distribution (V) and clearance (CL).
Relative bioavailability and bioequivalence
In pharmacology, relative bioavailability measures the bioavailability (estimated as the AUC) of a certain drug when
compared with another formulation of the same drug, usually an established standard, or through administration via a
different route. When the standard consists of intravenously administered drug, this is known as absolute
0.05 level of significance For FDA approval, a generic manufacturer must show that the 90% confidence interval for
the ratio of the mean response (usually AUC and Cmax) of its product to that of the "Brand Name drug" is within the
limits of 0.8 to 1.25 at the 0.05 level of significance. Relative bioavailability is extremely sensitive to drug
formulation. Relative bioavailability is one of the measures used to assess between two drug
products, as it is the Test/Reference ratio of AUC. The maximum concentration of drug in plasma or serum (Cmax)
is also usually used to assess bioequivalence. When Tmax is given, it refers to the time it takes for a drug to reach
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. As a result, in nutritional sciences, relative bioavailability or bioequivalence is the most common
measure of bioavailability, comparing the bioavailability of one formulation of the same dietary ingredient to
Factors influencing bioavailability
The absolute bioavailability of a drug, when administered by an extravascular route, is usually less than one (i.e.
<1). 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 the drug 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)
• The drug formulation (immediate release, excipients used, manufacturing methods, modified release - delayed
release, extended release, sustained release, etc.)
• Gastric emptying rate
• Interactions with other drugs/foods:
• Interactions with other drugs (e.g. antacids, alcohol, nicotine)
• Transporters: Substrate of an transporter? (e.g. P-glycoprotein)
• Enzyme induction (increase rate of metabolism). e.g. (antiepileptic) induces CYP1A2, CYP2C9,
CYP2C19 and CYP3A4
• Enzyme inhibition (decrease rate of metabolism). e.g. grapefruit juice inhibits CYP3A --> higher nifedipine
• Individual Variation in Metabolic Differences
• Age: In general, drugs metabolized more slowly in fetal, neonatal, and geriatric populations
• Phenotypic differences, enterohepatic circulation, diet, gender.
• Disease state
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 drug 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 and well-being; nutritional supplements do not exhibit characteristic
dose-response curves; and dosing intervals of nutritional supplements, therefore, are not critical in contrast to drug
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. In clinical trials with dietary supplements,
bioavailability primarily focuses on statistical descriptions of mean 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.
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 were included on products labels for example, make educated choices as to
the benefits of a formulation for 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.
 Griffin, J.P. The Textbook of Pharmaceutical Medicine (6th Ed.). New Jersey: BMJ Books. ISBN 9781405180351
 Factors Influencing the Measurement of Bioavailability, Taking Calcium as a Model. Robert P. Heaney. J. Nutr. (2001) 131:1344S-1348S
 Semple KT, Doick KJ, Jones KC, Burauel P, Craven A, Harms H (2004). "Defining bioavailability and bioaccessibility of contaminated soil
Environ. Sci. Technol. 38
doi:10.1021/es040548w. PMID 15260315.
 Shargel, L.; Yu, A.B. (1999). Applied biopharmaceutics & pharmacokinetics
(4th ed.). New York: McGraw-Hill. ISBN 0-8385-0278-4
 Heaney RP (2001). "Factors Influencing the Measurement of Bioavailability, Taking Calcium as a Model". J. Nutr. 131
 Srinivasan VS (2001). "Bioavailability of Nutrients: A Practical Approach to In Vitro Demonstration of the Availability of Nutrients in
Multivitamin-Mineral Combination Products". J. Nutr. 131
(4 Suppl): 1349S-1350S. PMID 11285352.
 The use of Isotopes in the Determination of Absolute Bioavailability of Drugs in Humans. Graham Lappin, Malcolm Rowland, R. Colin
Garner. Expert Opin. Drug Metab. Toxicol. (2006) 2(3)
 Biomedical accelerator mass spectrometry: recent applications in metabolism and pharmacokinetics. Graham Lappin, Lloyd Stevens. Expert
Opin. Drug Metab. Toxicol. (2008) 4(8):1021-1033
 Hoag SW, Hussain AS (2001). "The Impact of Formulation on Bioavailability: Summary of Workshop Discussion.". J. Nutr. 131
 Kagan D, Madhavi D, Bank G, Lachlan K (2010). ""Universal" and "Reliable" Bioavailability Claims: Criteria That May Increase Physician
Confidence in Nutritional Supplements.". Natural Medicine Journal. 2
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Coral Reefs (2011) 30:227–235 Assessing feeding electivity in Acanthaster planci: a nullmodel analysis M. Tokeshi • J. R. P. Daud Received: 8 February 2010 / Accepted: 26 October 2010 / Published online: 21 November 2010Ó Springer-Verlag 2010 Feeding electivity was investigated in a non- Acanthaster. The present study emphasizes the merit of outbreaking population of the crown-of-thorns starfish
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