Absorption and disposition kinetics of amoxicillin in normal human subjects

Pharmacokinetic parameters of amoxicillin were studied in healthy fasted subjects afqer both oral and intravenous administration of a single 500-mg dose. Serum levels and urinary excretion rates were determined at various time intervals by a microbiological method. The conventional two-compartment model with elimination occurring from the central compartment was used to analyze the data. Mean values were 3.40 h-1 for alpha and 0.68 h-1 for beta. Distribution constants kappa 12 and kappa 21 were 0.92 h-1 and 1.99 h-1, respectively. The rate constant for elimination from the central compartment, kappa 10, was 1.16 h-1. The volume of distribution was 20.2 liters (0.30 liter/kg), and the serum clearance was 13.3 liters/h. The absorption rate constant, kappa a, in the oral study, calculated by the Loo-Riegelman method, was 1.02 h-1, and the absorption half-life was 0.72 h. Absolute bioavailability after the oral dose was determined by comparing both the areas under the curve (AUC) and fractions of the antibiotic excreted unchanged in the urine. The AUC after oral administration was 77.4% of the intravenous AUC. On the other hand, recovery from the urine was 43.4% after the oral dose and 57.4% after the intravenous dose, indicating 76.5% bioavailability.