RENAL AND NONRENAL CLEARANCES OF CEFTRIAXONE AT THE STEADY-STATE AND ITS RELATION TO PLASMA-PROTEIN BINDING

The effect of the saturable plasma protein binding of ceftriaxone on t he 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 cef triaxone as the plasma concentration increased. The nonrenal clearance of the unbound ceftriaxone showed a statistically significant decreas e 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 clearance o f the unbound ceftriaxone was similar to the glomerular filtration rat e, which indicates that glomerular filtration is the principal mechani sm involved in the renal excretion of ceftriaxone in the sat.