What is bioavailability? Bioavailability of drugs

Bioavailability is the volume of a medicine that has reached its main place of action in the human or animal body. This term refers to the amount of lost and stored beneficial substances that have a beneficial effect on the body. Thus, with a high degree of bioavailability, one can judge the small number of lost medicinal properties of any drug.

How is this indicator determined?

With standard forms of research, the bioavailability of drugs is detected by determining the volume of the drug in the blood, that is, the amount that reaches the circulatory system. With various methods of administration, it has various indicators. So, with the intravenous method, bioavailability reaches 100%. And if there was an oral bioavailability, then the volume is significantly reduced due to incomplete absorption and breakdown of the drug into individual components.

This term is also used in pharmacokinetics to calculate the correct dosage, which should be followed by the patient with various methods of introducing the drug into the body.

There are two stages of bioavailability:

1. Absolute.
2. Relative.

The concept of absolute bioavailability

Absolute bioavailability is an indicator resulting from a comparative analysis of the bioavailability of a drug administered by any method other than intravenous and the availability of the drug administered intravenously. It is reflected in the form of the area under the curve "volume - time", abbreviated as "PPK". Such a procedure can only be carried out if a condition such as the use of various dosages by various methods of administration to the body is met.

To determine the amount of absolute bioavailability, a pharmacokinetic study is carried out, the purpose of which is to obtain a comparative analysis of the "volume of the drug in relation to time" for an intravenous and other method of introduction. Thus, the absolute bioavailability of drugs is PPC for the modified dosage obtained in the course of dividing the PPC of a different method of administration and intravenous.

The concept of relative bioavailability

Relative bioavailability is the PPC of a drug that has been compared with another variety of the same drug, taken as a basis or introduced in a different way. Basis is an intravenous route of administration characterized by absolute bioavailability.

To obtain data on the amount of relative bioavailability in the body, indicators are used that characterize the volume of the drug in the circulatory system or when it is removed from the body with urine after a single or multiple use. In order to obtain a high percentage of reliability in the analysis, a cross-sectional study method is used. It allows you to fully eliminate the difference in the results obtained with the physiological and pathological conditions of the body.

What techniques are used in determining bioavailability?

To determine whether the bioavailability of the drug is low or high, the following types of methods are used by scientists:

1. A comparative analysis of the changed volume of the drug between the studied and the main form of the drug in plasma or urine. Such a study allows you to fully determine the volume of absolute bioavailability.
2. Measuring the number of different drugs introduced into the body in the same way. This technique allows the determination of relative bioavailability.
3. Determination of the relative bioavailability by introducing drugs in various ways.
4. Examining the results of a drug or blood volume level. It is carried out to determine the indicator of relative bioavailability.

Benefits of HPLC

HPLC is another method for determining bioavailability - chromatography, which is highly effective in work, used when it is necessary to separate complex substances into simple ones. It is used most often in the study of bioavailability, as it has the following positive qualities:

1. The absence of limits on temperature resistance in the samples studied in this way.
2. It makes it possible to work with aqueous solutions, which significantly reduces the analysis time and improves the stage of preparation of biological samples.
3. The lack of need for derivatives of the studied drug.
4. The equipment used in this method of study has excellent performance and efficiency.

What can affect the overall bioavailability?

By default, the amount of the drug that is ingested by the non-intravenous route is less than 1. However, it may be even less due to some additional nuances. Thus, the factors affecting bioavailability are:

1. Physical properties of the drug.
2. The form of the drug and the duration of its effect on the body.
3. Reception time - before meals or after.
4. The speed of cleansing the gastrointestinal tract.
5. The effects of other drugs on this medicine.
6. The reaction means on some foods.

Bioequivalence

Another variety has bioavailability, it is bioequivalence. This concept arose in connection with pharmacokinetic and biopharmacy studies, during which it was found that the therapeutic inequality of drugs containing the same substances has a direct relationship with the difference in bioavailability.

Thus, bioequivalence is the provision of the blood and body tissues with the same amount of substances.

Key bioequivalence indicators

The following indicators are used to determine bioequivalence in preparations:

1. Increased or most complete bioavailability of tablets in the circulatory system. It is studied by compiling a graph in which two curves show the amount of drug administered by various methods, and a straight line indicates the minimum amount of drug required to obtain a therapeutic effect.
2. Duration of action of high drug content. This indicator displays the speed of absorption and therapeutic effects on the body. You can understand the whole essence of this indicator by the example of a sleeping pill. It will have a small therapeutic effect in half an hour or 2 - depending on the form of the drug. The sleeping pill will perform the therapeutic function, depending on the same form, from 5 to 8 hours. Thus, despite the similarity in its effect, one form will serve to prevent sleep disturbances, and the second - with a short rest time.
3. Change in the amount of medicine in the blood after a certain time.

Launching the drug into implementation

Before launching the drug on sale, one should study the bioequivalence and bioavailability of drugs, it is very important. To this end, the following procedure is carried out:

1. The manufacturer submits an application to the Pharmacological State Committee about the desire to release his medicine for sale. The agency, in turn, issues permission to conduct bioequivalence studies using two samples: an existing one and a new one.
2. The study is carried out on regular or with any disease volunteers in the same dosage. In addition, each study is paid by the manufacturer.

A similar procedure is being carried out in special medical institutions or laboratories with the involvement of third-party specialists. When selecting candidates for experiments, the following requirements should be taken into account:

1. Their total number cannot be less than 12. There are often times when the number of volunteers increases to 25. This mainly happens in the case of a high interindividual spread in pharmacokinetic parameters.
2. The age of the volunteers must be of legal age and not exceed 60 years.
3. The weight of each person should not be less than or more than 20% of the ideal weight for a given gender, age and height.
4. Research on people suffering from cardiovascular or chronic diseases is not allowed. The exception is the group of persons to whom the use of such a drug is recommended.

How are volunteers trained?

Before signing a consent to conduct a study determining the bioavailability of a substance, each volunteer should receive the following set of information:

1. The main objective of the study.
2. The duration of the procedure.
3. Basic pharmacological data on the drug.
4. The method of administering the drug inside.
5. The dosage used.
6. The effect of the drug on the body.
7. The disadvantages of this drug.
8. The nuances of nutrition during the study.
9. Terms of payment of insurance policy.

After the volunteer signs an agreement and non-disclosure agreement, the researchers carry out a full medical examination. It includes:

1. General examination by doctors.
2. Blood and urine tests.
3. Blood biochemistry.
4. A blood test for HIV, syphilis and hepatitis.
5. Definition of pregnancy in women.

Each chamber is equipped with everything necessary for convenient study. In addition, an agreement is concluded with any insurance company to obtain insurance in the event of an unsuccessful experiment. Additionally, conditions and the amount of remuneration are discussed.

Who is allowed to research?

Work with volunteers is carried out by a researcher. It must meet the following conditions:

1. The researcher must possess theory and practice in all chemical and pharmacological areas.
2. In his hands he should have a certificate of completion of courses.
3. The researcher should have a full understanding of what the bioavailability of the drug is (this is the main thing) and what kind of medicine it should study.

In addition to the researcher, the group should include nurses. Their responsibilities include:

1. Monitoring the health of patients.
2. Execution of regimen moments.
3. Installation of catheters.
4. The withdrawal of a certain amount of blood for analysis in patients.

Additionally, the group includes:

1. Analytics and laboratory assistants.
2. Pharmacokinetics
3. Mathematics.

Reporting on the work done

Upon completion of all research activities, the chief physician draws up a paper in which the following points should be reflected:

1. General plan for pharmacological research. It must be approved by the Pharmacological State Committee.
2. All data about volunteers. Demographic, anthropometric and clinical data should be indicated. The latter are indicated when patients are involved.
3. Series numbers and names of manufacturing companies, as well as the duration of their therapeutic effect.
4. The option of taking the drug and effective dosage.
5. The method of selection of biological material and its preliminary processing.
6. The sequence of presentation of analytics with the introduction of metrological indicators and demonstration chromotograms.
7. Full presentation of the entire course of the pharmacokinetic study and assessment of biological equivalence. All the programs used in the study are also indicated here.
8. The results of identifying the amount of drug in biological samples.
9. Volunteer medical records and individual profiles.
10. The results of a variance study of the pharmacokinetics used to evaluate biological equivalence.

Bioequivalence Procedure

The study on the bioavailability of drugs is carried out in the same dosage at once on two drugs: derivative and original. In the case of applications for the study of several drugs, the study is carried out separately for each.

The time interval between taking the generic and the original is determined by the duration of the movement of the drug in the body, the period of partial elimination. It should be equal to an average of 6 periods of partial elimination. The material used for the study may be plasma, serum, or blood. It is taken from a vein at the bend of the elbow through a catheter. Selection should be made three times:

1. At the time of the initial increase in the content of the drug. There should be about 3 points on the curve "concentration - time".
2. At the time of increased suction. About 5 points are applied.
3. At the time of reduced suction. About 3 points are used.

The study time can be considered acceptable if the area under the curve "concentration - time" at a distance from zero to the last sample takes about 80%.