Bioavailability is what? Bioavailability of medicinal substances

Bioavailability is the amount of a medicine that has reached its main place of action in the human or animal body. This term indicates the amount of lost and stored nutrients that have a beneficial effect on the body. Thus, with a high degree of bioavailability, it can be judged on the small number of lost therapeutic properties of any drug.

How is this indicator determined?

In standard forms of study, the bioavailability of drugs is detected by the method of determining the volume of the drug in the blood, that is, by the amount that reached the circulatory system. With different methods of administration, it has different indicators. Thus, with the intravenous method, bioavailability reaches 100%.And if there was oral bioavailability, the volume is significantly reduced due to incomplete absorption and disintegration of the drug into individual components.

This term is also used in pharmacokinetics to calculate the correct dosage, which should be adhered to the patient with various methods of administering 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, but intravenous, route and the availability of a drug administered intravenously. It is reflected in the form of the area under the curve "volume - time", abbreviated "PPK".Such a procedure can be carried out only if the condition is met, such as the use of different dosages by different methods of administration into the body.

To determine the amount of absolute bioavailability, a pharmacokinetic study is carried out, the aim of which is to obtain a comparative analysis of "drug volume versus time" for intravenous and other methods of implantation. Thus, the absolute bioavailability of drugs is an AUC for a changed dosage obtained during the division of PPC by another method of administration and intravenous.

The concept of the relative bioavailability of

Relative bioavailability is an AUC of a drug that has undergone a comparison with another variant of the same drug taken as a basis or otherwise administered. The basis is an intravenous route of administration characterized by absolute bioavailability.

To obtain data on the amount of relative bioavailability in the body, indicators characterizing the volume of a drug in the circulatory system or when it is excreted from the body together with urine after a single or multiple application are used. In order to obtain a high percentage of confidence in the analysis, a cross-method is used. It allows to eliminate as much as possible the difference in the results obtained under the physiological and pathological conditions of the organism.

What methods are used to determine bioavailability?

To determine if the bioavailability is low or high in the preparation, the following methods are used by scientists:

1. A comparative analysis of the altered drug volume between the studied and the main form of the drug in plasma or urine. Such a study allows to determine as much as possible the volume of absolute bioavailability.
2. Measurement of the number of different drugs administered in the body in the same way. This technique allows to determine the relative bioavailability.
3. Determination of the volume of relative bioavailability by introducing drugs in various ways.
4. Study of the results of the volume of the drug in the blood or urine. It is performed to determine the indicator of relative bioavailability.

Uses of HPLC

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

1. The absence of limits on the resistance to temperature in the samples thus studied.
2. Allows work with aqueous solutions, which significantly reduces the duration of analysis and improves the stage of preparation of biological samples.
3. No need to obtain derivatives of the study drug.
4. The equipment used in this method of study has excellent performance and efficiency.

What can affect the total bioavailability?

The standard volume of the drug that is ingested by the non-intravenous route is less than 1. However, it may be even smaller due to some additional nuances. Thus, the factors influencing bioavailability are:

1. Physical properties of the preparation.
2. The form of the medicine and the duration of its effects on the body.
3. Time of reception - before meals or after.
4. Speed ​​of cleansing of the gastrointestinal tract.
5. The effects of other drugs on this drug.
6. Reaction means for some food.

Bioequivalence of

Another species has bioavailability, it is bioequivalence. This concept has arisen in connection with the conduct of pharmacokinetic and biopharmaceutical 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 blood and body tissues with the same amount of substances.

Basic bioequivalence indicators for

The following indicators are used to determine bioequivalence in preparations:

1. Increased or most complete bioavailability of tablets in the circulatory system. It is investigated by drawing up a graph in which the two curves represent the amount of the drug administered by different methods, and the straight line indicates the minimum amount of medication necessary to obtain a therapeutic effect.
2. Duration of action of high drug content. This indicator reflects the speed of absorption and therapeutic effect on the body. Understand the whole essence of this indicator can be an example of a hypnotic drug. A small therapeutic effect, he will have in half an hour or 2 - depending on the form of the drug. The therapeutic function of sleeping pills will perform, depending on the same form, from 5 to 8 hours. Thus, despite the similarity in their impact, one form will serve to prevent sleep disturbances, and the second - for a short rest time.
3. Change in the amount of medication in the blood after a certain time.

Running a medicine into the implementation of

Before you start the drug on sale, you should study the bioequivalence and bioavailability of medicines, this is very important. To this end, the following procedure is followed:

1. The manufacturer submits an application to the State Pharmacological Committee about the desire to release its drug into the implementation. The Office, in turn, issues a permit to conduct bioequivalence studies using two samples: an existing one and a new one.
2. The study is carried out on ordinary or disease-bearing volunteers at the same dosage. Each research is paid by the manufacturer.

Such a procedure is carried out in special medical institutions or laboratories with the involvement of outside specialists. The following requirements must be taken into consideration when selecting the candidates for the experiments:

1. The total number can not be less than 12. It is not uncommon for the number of volunteers to increase to 25. This is mainly the case with a high interindividual dispersion in the pharmacokinetic parameters.
2. Age of volunteers must be of legal age and not be more than 60 years old.
3. The weight of each person should not be less than or greater than 20% of the ideal weight of for this sex, age and height.
4. It is not allowed to conduct research on people suffering from cardiovascular or chronic diseases. The exception is the group of people who recommend the use of such a drug.

How are volunteers trained?

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

1. The main objective of the study.
2. Duration of the procedure.
3. Basic pharmacological data on the preparation.
4. Method of drug administration inside.
5. The dosage used.
6. The effects of medication on the body.
7. Disadvantages of this drug.
8. Nuances of nutrition in the process of research.
9. Terms of payment of insurance policy.

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

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

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

Who is allowed to research?

The work with volunteers is carried out by the researcher. It must meet the following conditions:

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

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

1. Monitoring the health of patients.
2. Execution of mode moments.
3. Installation of catheters.
4. Taking some blood for analysis in patients.

In addition to the group include:

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

Drawing up a report on the work performed

After completing all the research activities, the chief doctor prepares a paper, which should reflect the following points:

1. General plan for pharmacological research. It must necessarily 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. Numbers of series and names of manufacturing companies, as well as the duration of their therapeutic effect.
4. Drug administration and effective dosage.
5. Method of selection of biological material and its pre-processing.
6. Sequence of presentation of analytics with the introduction of metrological indicators and demonstration chromatograms.
7. Complete description of the entire course of the pharmacokinetic study and evaluation of biological equivalence. Here all the programs used in the study are indicated.
8. Results of the detection of the amount of the drug in biological samples.
9. Medical cards of volunteers and individual profiles.
10. Results of a variance study of the pharmacokinetics values ​​used to assess biological equivalence.

Sequence of actions for bioequivalence of

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

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

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

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