Bioavailability of new formulations of amoxicillin in relation to its absorption kinetics

The newly developed amoxicillin (Flemoxin) formulations, a film-coated tablet (A) and an effervescent tablet (B) were tested for bioavailability against a commercial reference formulation (C). The content of amoxicillin in each formulation was 1000 mg. The cross-over study involved 12 healthy volunteers. Blood samples were taken at 10 time intervals after administration and plasma analysed for amoxicillin concentration by bio-assay. Numerically, the effervescent formulation had a superior mean bioavailability over both other formulations, but the difference failed to reach statistical significance due to quite large individual variations. A striking point emerging from a pharmacokinetic treatment of the data was the zero-order nature of the amoxicillin absorption. Re-evaluation of some published data on amoxicillin serum or plasma concentrations, with sufficient data points in the absorption phase, confirmed this observation. This absorption behaviour of amoxicillin is discussed. Assuming the same volume of distribution of amoxicillin for the three formulations, it could be calculated that the mean zero-order rate constant for the effervescent formulation B exceeded that for formulations A and C by a factor of 1.9 and 1.5, respectively. Thus, formulation B shows the most rapid absorption of amoxicillin in accordance with its administration in an already dissolved form.