Bioavailability is what? Bioavailability of medicinal substances

Bioavailability is the amount of medicine that has reached its main place of action in the human or animal body. This term denotes the number of lost and stored nutrients that have a beneficial effect on the body. Thus, with a high degree of bioavailability, it is possible to judge the small number of the lost medicinal 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". To carry out a similar procedure is possible 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 purpose 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 AUC for the changed dosage obtained during the division of PPC by another method of administration and intravenous.

The concept of relative bioavailability

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 you to completely eliminate the difference in the results obtained under the physiological and pathological conditions of the body.

What methods are used to determine bioavailability?

To determine the low bioavailability in the preparation or high, scientists use the following types of techniques:

1. Comparative analysis of the altered 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 amount 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. A 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.

Pros of using HPLC

HPLC - 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 studied in this way.
2. It allows working 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 amount of bioavailability?

Typically, the 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 that affect bioavailability are:

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

Bioequivalence

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 revealed 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.

Main indicators of bioequivalence

The following indicators are used to determine bioequivalence in preparations:

1. Increased or most complete bioavailability of tablets in the circulatory system. It is explored by drawing a graph in which the two curves show the amount of the drug administered by different methods, and the straight line indicates the minimum amount of medication required to produce 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 medicine in the blood after a certain time.

Running the medicine into the implementation

Before you start the drug on sale, you should study the bioequivalence and bioavailability of medicines, it 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 medicine 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 in 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. When selecting candidates for experiments, the following requirements should be taken into account:

1. Their 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. The age of volunteers must be of legal age and not exceed 60 years.
3. пола, возраста и роста. The weight of each person should not be less or more than 20% of the ideal weight for a given 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 an agreement to conduct a study determining the bioavailability of the substance, each volunteer should receive the following set of information:

1. The main task of the study.
2. Duration of the procedure.
3. Basic pharmacological data on the preparation.
4. Method of administration of the drug inside.
5. The dosage used.
6. The effect 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. Analysis of blood and urine.
3. Biochemistry of blood.
4. Blood test for HIV, syphilis and hepatitis.
5. Determination of pregnancy in women.

Each room is equipped with everything necessary for convenient 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 amount of remuneration are negotiated.

Who is allowed to research?

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. On his hands he must have a certificate of completion of the courses.
3. The researcher should have a full 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 regime moments.
3. Installation of catheters.
4. Taking some blood for analysis in patients.

Additionally, the group includes:

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

Reporting on the work done

Upon completion of all research activities, the chief doctor prepares a paper in which the following points should be reflected:

1. General plan of pharmacological studies. 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. Number of series and names of manufacturing companies, as well as the duration of their therapeutic effect.
4. Variant of drug administration and effective dosage.
5. Method of selection of biological material and its pre-processing.
6. The sequence of presentation of the analysts with the introduction of metrological indicators and demonstration chromatograms.
7. Complete presentation of the entire course of the pharmacokinetic study and evaluation of biological equivalence. Here you can find all the programs used in the study.
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 the variance study of the pharmacokinetics values used to assess biological equivalence.

Sequence of actions for bioequivalence

The study of the bioavailability of drugs is carried out 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 the reception of the generic and the original is determined by the duration of movement of the drug 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. Selection should be done three times:

1. At the time of primary growth of 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 absorption. Uses 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 occupies about 80%.