Bioavailability is the volume of a drug that has reached its primary site of action in the human or animal body. This term refers to the amount of lost and retained nutrients that have a beneficial effect on the body. Thus, with a high degree of bioavailability, one can judge a small amount of lost medicinal properties of any drug.
How is this indicator determined?
In standard forms of research, the bioavailability of drugs is determined by determining the volume of the drug in the blood, that is, the amount that has reached the circulatory system. With different methods of administration, it has different indicators. So, with the intravenous method, bioavailability reaches 100%. And if there was oral bioavailability, then 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 that the patient should adhere to at various administration methods.drug into the body.
There are two stages of bioavailability:
- Absolute.
- Relative.
The concept of absolute bioavailability
Absolute bioavailability is a measure resulting from a comparative analysis of the bioavailability of a drug administered by any route other than intravenous administration and the availability of a drug administered intravenously. It is reflected as the area under the volume-time curve, abbreviated as AUC. Such a procedure can be carried out only if such a condition is met as the use of different dosages by different methods of introduction 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 the "volume of drug in relation to time" for intravenous and other methods of administration. Thus, the absolute bioavailability of drugs is the AUC for the modified dosage obtained by dividing the AUC of a different route of administration and intravenous.
The concept of relative bioavailability
Relative bioavailability is the AUC of a drug when compared to another version of the same drug, taken as a base or otherwise administered. The base is an intravenous route of administration, characterized by absolute bioavailability.
To get data on quantityrelative bioavailability in the body, indicators are used that characterize the volume of the drug in the circulatory system or when it is excreted 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 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 whether a drug has low or high bioavailability, scientists use the following types of techniques:
- Comparative analysis of the altered volume of the drug between the study and the main form of the drug in plasma or urine. Such a study allows you to fully determine the amount of absolute bioavailability.
- Measurement of the amount of different drugs introduced into the body in the same way. This technique allows you to determine the relative bioavailability.
- Determination of the amount of relative bioavailability by introducing drugs in various ways.
- Studying the results of the level of drug volume in the blood or urine. Performed to determine the relative bioavailability index.
Advantages of using HPLC
HPLC - another method for determining bioavailability - chromatography, which is highly efficient in operation, 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:
- No limits on temperature resistance for samples studied in this way.
- Enables working with aqueous solutions, which significantly reduces analysis time and improves the preparation of biological samples.
- No need to derivatize study drug.
- The equipment used in this study method has excellent performance and efficiency.
What can affect overall bioavailability?
Standardly, the volume of the drug that enters the body by a non-intravenous route is less than 1. However, it can be even less due to some additional nuances. Thus, the factors affecting bioavailability are:
- Physical properties of the drug.
- The form of the drug and the duration of its effect on the body.
- Time to take - before meals or after.
- Quick cleansing of the gastrointestinal tract.
- The effect of other drugs on this drug.
- Reaction of funds to some foods.
Bioequivalence
Another variety has bioavailability, this is bioequivalence. This concept arose 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 directrelationship with the difference in bioavailability.
Thus, bioequivalence is the provision of the blood and tissue of the body with the same amount of substances.
Key Bioequivalence Indicators
The following indicators are used to determine bioequivalence in drugs:
- Increased or most complete bioavailability of tablets in the circulatory system. Investigated by drawing up a graph in which two curves represent the amount of drug administered by various methods, and a straight line represents the minimum amount of drug required to obtain a therapeutic effect.
- Duration of high drug content. This indicator reflects the rate of absorption and therapeutic effects on the body. You can understand the whole essence of this indicator using 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. Sleeping pills will perform a 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.
- Change in the amount of drug in the blood after a certain time.
Drug launch
Before you launch the drug on sale, you should study the bioequivalence and bioavailability of drugs, this is very important. To this end, the following procedure is carried out:
- Manufacturer applies forPharmacological State Committee about the desire to release their medicine for sale. The agency, in turn, issues permission to conduct bioequivalence studies using two samples: an existing one and a new one.
- The study is carried out on normal or diseased volunteers at the same dosage. In addition, each study is paid by the manufacturer.
A similar procedure is 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:
- Their total number cannot be less than 12. It is not uncommon for the number of volunteers to increase to 25. This mainly happens in the case of a high inter-individual variation in pharmacokinetic parameters.
- Volunteers must be of legal age and under 60.
- 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.
- Research on people with cardiovascular or chronic diseases is not allowed. The exception is the group of people who are recommended to use such a drug.
How are volunteers trained?
Before signing consent to conduct a study that determines the bioavailability of a substance, each volunteer must receive the following kitdetails:
- The main task of the study.
- Duration of the procedure.
- Basic pharmacological data about the drug.
- Method of drug administration by mouth.
- Applied dosage.
- The effect of the drug on the body.
- Disadvantages of this drug.
- Nutritional nuances under investigation.
- Terms of payment of the insurance policy.
After the volunteer signs the contract and non-disclosure agreement, the researchers perform a full medical examination. It includes:
- General examination by doctors.
- Blood and urine tests.
- Blood biochemistry.
- Blood test for HIV, syphilis and hepatitis.
- Determination of pregnancy in women.
Each room is equipped with everything you need for a comfortable study. In addition, an agreement is concluded with any insurance company to receive insurance in case of an unsuccessful experiment. Additionally, the conditions and amount of remuneration are discussed.
Who is allowed to study?
Work with volunteers is carried out by the researcher. It must meet the following conditions:
- The researcher must have theory and practice in all chemical and pharmacological areas.
- He must have a course completion certificate in his hands.
- The researcher must have a complete understanding of what the bioavailability of the drug is (this is the main thing) and which drug he should study.
In addition to the researcher, the group should includenurses. Their duties include:
- Monitoring the he alth of patients.
- Performance of regime moments.
- Installation of catheters.
- Withdrawing some blood for analysis from patients.
Additionally, the group includes:
- Analysts and laboratory assistants.
- Pharmacokinetics.
- Math.
Writing a progress report
At the end of all research activities, the chief physician draws up a paper in which the following points should be reflected:
- General plan for pharmacological research. It must be approved by the Pharmacological State Committee.
- All data about volunteers. Demographic, anthropometric and clinical data should be provided. The latter are indicated when patients are involved.
- Batch numbers and names of manufacturing companies, as well as the duration of their therapeutic effect.
- Drug options and effective dosage.
- Method of selecting biological material and its preliminary processing.
- The sequence of presentation of analytics with the introduction of metrological indicators and demonstration chromatograms.
- Full summary of the entire course of the pharmacokinetic study and assessment of biological equivalence. All programs used in the study are also indicated here.
- Results of the detection of the amount of the drug in biological samples.
- Volunteer medical records and individual profiles.
- Results of the dispersion studypharmacokinetic 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 on two drugs at once: a derivative and an 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 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 can be plasma, serum or blood. It is taken from a vein in the crook of the elbow through a catheter. Selection must be made three times:
- At the time of the primary growth of the drug content. There should be about 3 points on the concentration-time curve.
- At the moment of increased suction. About 5 points applied.
- At the moment of reduced suction. About 3 points are used.
The study time can be considered acceptable if the area under the concentration-time curve from zero to the last sample is about 80%.
