Two tablets of the same medicine, with the same nominal dose , can deliver significantly different amounts of the active substance into the bloodstream. The same molecule given orally and intravenously can work with a strength that differs several times. that organizes these differences is bioavailability .
Bioavailability describes how much of the administered dose reaches the general circulation unchanged and at what rate . It is determined not only by the properties of the molecule itself , but also by the form of the drug, the route of administration, the physiology of the digestive tract and the liver, which metabolizes part of the dose before it reaches the target tissues . This is why the dose written on the package and the amount of the drug that will actually work, These are two different sizes.
What does it actually mean that a drug is "available"
Bioavailability is usually denoted by the symbol F and expressed as a fraction or percentage. The reference point is intravenous , IV administration , at which the entire dose by definition goes into the circulation, so its bioavailability is 100%. Any other route of administration is compared with this pattern.
Two types of this indicator are distinguished . Absolute bioavailability compares a given route of administration, usually oral, with intravenous administration of the same substance. Relative bioavailability compares two preparations administered by the same route, For example , a new tablet with a reference preparation. The latter concept underlies the evaluation of generic drugs , which we will return to later.
How bioavailability is measured
The measurement is based on a curve of the dependence of the concentration of the drug in the blood over time. The key parameter is the area under the curve (AUC), which reflects the body's total exposure to the drug. The other two are the maximum concentration (Cmax), indicating the strength of the peak effect, and the time of its attainment (Tmax), indicating the rate of absorption.
Absolute bioavailability is calculated as the ratio of the fields under the curve after administration by the test route and intravenously, corrected for doses:
F = (AUC_doustne × dawka_iv) / (AUC_iv × dawka_doustna)
The F value alone does not tell the whole story. A modified-release formulation may have the same AUC as the immediate-release formulation , but still have a different activity profile : lower and later Cmax, longer time of maintaining the therapeutic concentration . Therefore , when evaluating a drug, the quantity and the rate are looked at in parallel , because they together shape the clinical effect .
The first pass effect : why part of the dose disappears
When taken orally , the drug does not go straight into the general circulation . Once absorbed from the lumen of the intestine, blood from most of the digestive tract flows through the portal vein to the liver before reaching the heart and the rest of the body. And often earlier, in the intestinal wall, some molecules are metabolized. This phenomenon is called the first-pass effect.
Cytochrome P450 enzymes , in the intestine mainly CYP3A4, and P-glycoprotein (P-glycoprotein, P-gp), a transport protein that pumps part of the absorbed drug back into the lumen of the intestine, are responsible for the losses in this section . In the liver, other P450 isoenzymes and coupling reactions , including glucuronidation and sulfation. The sum of these processes can consume most of the dose before anything works.
