Bioavailability (BA): The amount of drug that reaches the systemic circulation from an administered dosage and the rate at which the drug appears in the systemic circulation are referred to as bioavailability. The extent and rate at which the active moiety (drug or metabolite) enters systemic circulation, allowing it to reach the site of action, is referred to as bioavailability. The qualities of the dosage form, which are partly dictated by its design and manufacture, play a big role in a drug's bioavailability.
Because differences in bioavailability among medication formulations can have clinical implications, it's critical to determine whether they're equal. Chemical equivalency means that medicine goods contain the same active chemical in the same proportion and meet current government requirements; nevertheless, drug products' inactive constituents may differ. When given to the same patient in the same dose regimen, bioequivalence means that the drug products produce similar drug concentrations in plasma and tissues.
Therapeutic equivalence means that drug products have the same therapeutic and unfavorable effects when administered to the same patient in the same dosing regimen. Therapeutically, bioequivalent products are expected to be the same. When patients who have been stabilized on one formulation are offered a non-equivalent alternative, therapeutic non-equivalence (e.g., more side effects, less efficacy) is frequently observed during long-term treatment. Despite discrepancies in bioavailability, therapeutic equivalency is sometimes feasible. Penicillin, for example, has such a large therapeutic index (the ratio of the minimum dangerous concentration to the median effective concentration) that modest changes in plasma levels due to bioavailability variances in penicillin products have little effect on efficacy and safety. Bioavailability discrepancies, on the other hand, might create significant therapeutic non-equivalence for medicines with a limited therapeutic index.
What is Bioequivalence(BE) Studies?
Bioequivalence (BE): When delivered at the same molar dose, bioequivalence of a drug product is attained if the extent and rate of absorption are not statistically significantly different from those of the reference product. Bioequivalence studies examine two medications or two formulations of the same drug to show that their bioavailability and PK/PD parameters are substantially comparable.
These studies are frequently conducted for generic medications or when a drug's composition is altered during development. Typically, what is needed to demonstrate equivalence from a regulatory viewpoint is to show that the experimental drug's PK profile falls within 20% of the reference drug. The 20% is an arbitrary number but is satisfactory for the majority of drugs. In some cases, for drugs with a narrow therapeutic index such as warfarin, 20% may be too large. Practically, what this means is that the upper limit of 95% confidence interval for the experimental drug must fall below 125% of the reference drug and the lower limit must fall above 80% of the reference drug. A value of 125% is used because the difference between 125 and 100 is 20% if one uses 125 as the denominator. Confidence interval is used because it is important that the drug is less than 20% different. If point estimate is used without confidence intervals, then a drug with very wide variability that on average is within 20% of the reference drug but quite often falls outside of that could be considered to be equivalent.