Capacity-limited elimination of cefmetazole in rat

Elimination kinetics of cefmetazole (CMZ) in the rat is studied with changing the dosing amount (D). The normalized area under plasma concentration-time curve (AUC/D) and the mean residence time (MRT) increase with increasing amount of i.v. dose of CMZ. These increases prove the capacity-limited elimination of CMZ without regard to any pharmacokinetic model. The apparent steady-state volume of distribution (V^a_ss) which is defined by D β MRT/AUC is almost independent of D. The simultaneous multi-lines fitting using time course curves following different doses is also attempted to determine the pharmacokinetic model by the application of the minimum AIC estimation (MAICE). AIC, consequently, shows the minimum for the two-compartment model with the Michaelis-Menten elimination. The Y_ss estimated from this model is about 450 ml/kg which agrees with V^a_ss estimated by moment analysis.