The degree and speed with which an active form (the drug or one of its metabolites) accesses the circulation and thus reaches its place of action is called bioavailability.The bioavailability of a drug depends largely on the properties of the pharmaceutical form, which in turn depend in part on its design and manufacture described by Bioequivalence Study in Canada. The bioavailability differences between different formulations of the same drug may have clinical importance; Therefore, it is essential to know whether different formulations of a drug are equivalent or not.
Chemical equivalence implies that two pharmacological products contain the same amount of the same active compound and comply with the official requirements in force; however, they may differ in their content in inactive ingredients. Bioequivalence means that these pharmacological products give rise to equivalent concentrations of the drug in plasma and tissues when administered to the same patient using the same dosages. The therapeutic equivalence indicates that these products cause the same therapeutic and adverse effects when administered to the same patient using the same dosage.
In principle, bioequivalent products are also therapeutically equivalent. The absence of therapeutic equivalence (e.g., more adverse effects, less efficacy) is usually discovered by administering a new non-equivalent drug with another formulation to a patient in chronic treatment who was stable.
Causes of low Bioavailability
Many drugs can be metabolized before an adequate plasma concentration is reached. The low bioavailability is more frequent with oral dosage forms of low water-soluble drugs that are absorbed slowly.
Another important cause of low bioavailability is not having enough time in the digestive tract for absorption to occur. If the drug does not dissolve easily or is unable to cross the epithelial membrane (e.g., if it is highly ionized and polar), the residence time at the absorption sites may be insufficient. In these cases, besides being low, bioavailability is usually very variable.
Bioequivalence Study in Canadasearched that the bioavailability of a drug can also be affected by age, sex, physical activity, genetic phenotype, stress, disease (e.g., achlorhydria, malabsorption syndromes).
Chemical reactions that reduce absorption can also decrease bioavailability. These include complex formation (e.g., between tetracyclines and polyvalent metal ions), hydrolysis by gastric acid or digestive enzymes (e.g., hydrolysis of penicillin or chloramphenicol palmitate), conjugation in the intestinal wall (e.g., isoproterenol sulfoconjugation), adsorption to other drugs (e.g., digoxin to cholestyramine) and metabolism by the microflora of the intestinal lumen.
Bioavailability Calculation
Bioavailability is usually calculated by determining the area under the plasma concentration-time curve (ABC see Representation of the relationship between plasma concentration and time after oral administration of a single dose of a hypothetical drug.). The most reliable parameter of the bioavailability of a drug is ABC. The ABC is directly proportional to the total amount of unmodified drug that reaches the systemic circulation. Pharmaceutical products can be considered bioequivalent in terms of magnitude and rate of absorption if their plasma concentration curves are practically superimposable.
The plasma concentration of the drug is higher the higher the absorption; the maximum plasma concentration (peak) is reached when the elimination rate and absorption rate are equalized. The calculation of bioavailability by determining the maximum plasma concentration can lead to errors, since the elimination of the drug begins from the moment it enters the bloodstream. Peak time (when the maximum plasma concentration of the drug occurs) is the most frequently used parameter to calculate the rate of absorption; The slower it is, the peak is reached later.
The bioavailability of drugs that are excreted primarily by the urinary tract without having undergone modifications can be estimated by measuring the total amount of drug excreted after the administration of a single dose. Ideally, to recover in the urine all the drug that has been absorbed, urine is collected for a time 7-10 times greater than the elimination half-life of the drug. When multiple doses have been administered, bioavailability can be calculated by measuring the amount of intact drug recovered from the urine over a period of 24 hours.
