Bioequivalence and Bioavailability Forum

Hi John & Ohlbe,

❝ It is possible if he is talking about a ER q.d. vs IR b.i.d (or t.i.d, or q.i.d.) formulation under the same total daily dose where in some cases one might want to demonstrate bioquivalence between the two products. Example, Ultram ER is bioequivalent to Tramadol IR (given as qid)....

CFR 21(5) §320.1

(a) Bioavailability means the rate and extent to which the active ingredient or active moiety is absorbed from a drug product and becomes available at the site of action.

Already this definition sends pharmacokineticists through the ceiling. According to the book, BA means only the AUC (strictly speaking the AUC_0–∞ or AUC_0–τ). There is no “rate of BA” in PK.

(e) Bioequivalence means the absence of a significant difference in the rate and extent to which the active ingredient or active moiety in pharmaceutical equivalents or pharmaceutical alternatives becomes available at the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study. Where there is an intentional difference in rate (e.g., in certain extended release dosage forms), certain pharmaceutical equivalents or alternatives may be considered bioequivalent if there is no significant difference in the extent to which the active ingredient or moiety from each product becomes available at the site of drug action. This applies only if the difference in the rate at which the active ingredient or moiety becomes available at the site of drug action is intentional and is reflected in the proposed labeling, is not essential to the attainment of effective body drug concentrations on chronic use, and is considered medically insignificant for the drug.

So, given the blue part, John is right.