Modeling of the saturable time-constrained amoxicillin absorption in humans.

Amoxicillin pharmacokinetics was modeled using a two-compartment disposition model and a saturable time-constrained absorption model with a storage compartment. The absorption model parameters estimated by the nonlinear regression are: a rate constant of the systemic input, ksys, (median: 1.31 h-1, range: 0.79-7.01 h-1), a maximal absorption rate, Vmax (median: 1407 mg/h, range: 703-4181 mg/h), an account corresponding to the half maximal rate, Kma, (median: 1077 mg, range: 235-4376 mg), time of the absorption cessation, Tabs, (median: 1.72 h, range: 0.82-4.53 h) and absorption lag time. Tlag, (median: 0.085 h, range: 0-0.123 h). It was shown, that the first-order absorption parallel to the saturable process is negligible in the dose range studied. The model described well the dependence of areas under concentration-time curves on the dose determined in several earlier studies. It was used also to predict the fraction of the amoxicillin dose absorbed for different doses. Simulations performed over a wide dose range (50-10000 mg) demonstrated that the fraction absorbed decreases nonlinearly from 90% at 50 mg to 22% at 10000 mg and strongly depends on the duration of the absorption period.