Dose dependence in human absorption of aminopenicillins

Abstract

The concentration of antibiotic in a focus of infection depends both on the peak serum concentration and on the area under the serum concentration time curve (AUC). A knowledge of the relationship between increased doses and the corresponding response in serum concentration would be relevant as a basis for determining an adequate clinical dosage. Dose-related changes in the two pharmacokinetic variables, peak serum concentration and AUC, after single doses of bacampicillin are compared with data on different aminopenicillins from other studies. With ampicillin there is a nonlinear relationship between both dose-peak and dose-AUC. The results indicate that the poor absorption of oral ampicillin can only be partially compensated for by increasing the oral dose. But with amoxycillin and the ampicillin esters the absorbed amount (AUC) is a linear function of the dose in the dosage range investigated. The increase in peak serum level with high doses of oral ampicillin is far less than proportional, while this tendency was less pronounced for amoxycillin and still less for pivampicillin, talampicillin and bacampicillin.