Renal and nonrenal clearances of ceftriaxone at the steady-state and its relation to plasma protein binding

Abstract The effect of the saturable plasma protein binding of ceftriaxone on the elimination of this drug was studied under steady-state conditions in the rat. A concentration-dependent increase in the total, renal and nonrenal clearances of total drug (bound + unbound) was observed, and it was related to the increase in the ex vivo unbound fraction of ceftriaxone as the plasma concentration increased. The nonrenal clearance of the unbound ceftriaxone showed a statistically significant decrease as the plasma concentration of the unbound drug at the steady state increased, which indicates that the nonrenal elimination of the drug (mainly by biliary excretion) is a saturable process. Renal c…