Bioavailability refers to the degree and rate at which the active portion (drug or metabolite) enters the general circulation, and so is available at the site of action.
(See also Overview pharmacokinetics.) Bioavailability refers to the extent and rate at which the active part (drug or metabolite) enters the systemic circulation and thus available at the place of action. The bioavailability of a drug is determined largely by the properties of the dosage form, partly dependent on the design and the manufacture. The differences in bioavailability between the different formulations of a drug may be clinically significant. It is therefore essential to know which drug formulations are equivalent. However, the inactive ingredients between the finished products may differ. Chemical equivalence means that drug-finished products contain the same active ingredient in the same amount and same meet current valid official standards. Bioequivalence means that the drug-finished products that achieve equivalent drug concentrations in plasma and tissues, if given the same patient with the same dosing schedule. Therapeutic equivalence means that drug products at the same therapeutic effect and same undesirable effects result when they are given the same patient with the same dosing schedule. Of bioequivalent products is expected to equivalent therapeutic. Therapeutic nonequivalence (z. B. more adverse effects, lower efficiency) is usually detected at a long-term treatment, when patients are set to a formulation obtained a non-equivalent replacement. Sometimes therapeutic equivalence is possible despite differences in bioavailability. For example, the therapeutic index (ratio of the minimum toxic concentration at the median effective concentration) with penicillin so high that usually have moderate differences in plasma concentration, based on differences in the bioavailability of penicillin products will not affect the efficacy and safety. In contrast, differences in the bioavailability of medicinal products can lead to a low therapeutic index in a significant therapeutic non-equivalence. Reasons for a low bioavailability drug that are administered orally, the intestinal wall and must pass then pass through the portal vein to the liver enter. Both are common places of first-pass metabolism (metabolism before a drug reaches the systemic circulation). Therefore, numerous drugs are metabolized before adequate plasma concentrations are reached. A low bioavailability is often observed together with oral dosage forms of poorly water-soluble drugs that are absorbed slowly. A common cause of low bioavailability is lack of time for absorption in the gastrointestinal tract. If the drug dissolves poorly or can not penetrate the epithelial membrane (z. B. because it heavily loaded and is polar), the time may be insufficient at the absorption site. In such cases, there is a tendency to an equally highly variable such as low bioavailability. Age, sex, physical activity, genetic phenotype, stress, disease (eg. As stomach acid deficiency, malabsorption syndrome) or previous surgery of the gastrointestinal tract (eg. As bariatric surgery) can also affect the bioavailability of a drug. Chemical reactions that reduce the absorption can reduce bioavailability. They include complex formation (eg., Between tetracycline and polyvalent metal ions) hydrolysis by gastric acid or digestive enzymes (eg., Penicillin, chloramphenicol palmitate hydrolysis) conjugation in the gut wall (for. Example, sulfoconjugation of isoproterenol), adsorption other drugs (e.g., digoxin to cholestyramine), and metabolism by the microflora in the intestinal lumen. Measuring the bioavailability The bioavailability is usually by determining the area under the curve in which the plasma concentration is plotted versus time (AUC, area under curve, plasma concentration curve – Representative relationship between plasma concentration at time after administration of a single oral dose of a hypothetical drug.) , AUC is the most reliable measure of the bioavailability of a drug. The AUC is directly proportional to the total amount of unchanged drug that reaches the systemic circulation. Medicines finished products may be considered bioequivalent in terms of extent and rate of absorption if their plasma concentration curves basically cover. Representative relationship between plasma concentration at time after administration of a single oral dose of a hypothetical drug. The plasma concentration of the drug increases with the extent of absorption. The maximum plasma concentration (peak value) is reached when the rate of elimination of the drug is equal to the rate of absorption. Provisions of the bioavailability based on the maximum plasma concentration can be misleading, because the elimination of the drug used immediately after its entry into the bloodstream. The timing of the peak value (when the maximum plasma concentration of the drug is reached) is the most common general indication of the rate of absorption. The slower the absorption takes place, the later is the time of the peak value. For medicinal products which are excreted primarily unchanged in the urine, the bioavailability can be determined by dividing the total amount excreted is measured after a single dose. Ideally, the urine is collected over 7 to 10 elimination half-times in order to obtain a complete urine yield of the absorbed drug. After multiple doses, the bioavailability can be determined by the recovered in 24-h urine volume is measured on the natural drug under equilibrium conditions.