THE RENAL CLEARANCE OF CEFUROXIME AND CEFTAZIDIME AND THE EFFECT OF PROBENECID ON THEIR TUBULAR EXCRETION

1 The renal tubular excretion of cefuroxime and ceftazidime in relatio n to the coadministration of probenecid was investigated in eight and two healthy subjects, respectively. 2 Cefuroxime or ceftazidime were a dministered by i.v. infusion and 1 g probenecid was administered orall y after steady state plasma concentrations of the cephalosporin were r eached. 3 In a second session the same antibiotic was administered at increasing infusion rates such that three different levels of plasma d rug concentration were achieved. 4 The renal clearance of antibiotic w as calculated based upon unbound plasma concentration, and tubular cle arance was estimated by subtracting inulin clearance from the renal cl earance of the antibiotic. 5 Non-linear regression analysis was used t o estimate parameters describing the saturability of tubular excretion and the effect of probenecid inhibition, i.e. EC(50) and R(tub),(max) , could be established for cefuroxime: EC(50) was 248 (s.d. 130) mg1(- 1) and R(tub),(max) was 1.852 (s.d. 0.577) mg h(-l). Tubular excretion of ceftazidime was practically zero. The EC(50) Of probenecid for inh ibition of the tubular excretion of cefuroxime was 0.80 (s.d. 0.31) mg 1(-1). 6 The results indicate that in the therapeutic plasma concentra tion range of cefuroxime its renal clearance is not saturated. Probene cid at therapeutic doses will block tubular excretion of cefuroxime al most completely.