Renal disposition of ceftazidime illustrated by interferences by probenecid, furosemide, and indomethacin in rabbits

Abstract

Excretion of ceftazidime (C), a new cephalosporin antibiotic, has been reported to occur unexpectedly through glomerular filtration only, without being significantly affected by probenecid. We investigated renal tubular disposition of C in rabbits by calculating its rates of fractional excretion, net tubular secretion, and absolute excretion. During continuous intravenous infusion of C, 3 mg of furosemide (F), 15 mg of probenecid (P), or 2 mg of indomethacin (I) per kg was injected intravenously as a bolus. Equilibrium dialysis showed that the percentage of C bound to serum proteins (14 +/- 5%) was not altered by F, P, or I. Fractional excretion of C was 94 +/- 22, 65 +/- 21, 182 +/- 36, and 98 +/- 3% for the drug given alone and after injection of F, P, and I, respectively. For 15 min after P injection, we observed net tubular secretion of C (404 +/- 276 micrograms/min). The C absolute excretion rate was significantly reduced by I compared with the absolute excretion rate for the control (405 +/- 104 versus 696 +/- 157 micrograms/min). We conclude that (i) C undergoes bidirectional transport in the nephron, revealed by the effects of F and P, with a nil net C balance; (ii) F and P have opposite unexpected effects on tubular handling of C, possibly due to competition for C secretion processes; (iii) I reduces C excretion solely by decreasing its glomerular-filtered load; and (iv) tubular handling of C differs from that of previously studied cephalosporins.