Vancomycin pharmacokinetics, renal handling, and nonrenal clearances in normal human subjects

Publisher Website
Google Scholar
Abstract
The renal handling of vancomycin is unknown. Previously reported studies have not achieved steady-state conditions with constant vancomycin concentrations. We measured systemic vancomyin clearance simultaneously with the renal clearances of vancomycin, creatinine, inulin, and para-aminohippurate in nine healthy subjects at steady-state serum vancomycin concentrations of 7 and 14 mg/L. For all steadystate observations the renal clearance of vancomycin was 89 .+-. 11 ml/min (mean .+-. SE), the clearance of inulin 105 .+-. 9 ml/min, the clearance of creatinine 117 .+-. 9 ml/min, and the clearance of paramainohippuric acid 496 .+-. 41 ml/min. The systemic clearance of vancomycin was 131 .+-. 7 ml/min. The clearances of creatinine, inulin, and para-aminohippuric acid and the renal clearance of vancomycin were not statistically different at both steady-state vancomycin concentrations. The ratio of the renal clearance of vancomycin to the clearance of inulin was 0.89 .+-. 0.06 and to creatinine clearance 0.79 .+-. 0.05. Both ratios were independent of vancomycin concentration, urine flow rate, and filtration fraction. The systemic clearance of vancomycin was 10% greater at serum vancomycin concentrations of 14 mg/L than at 7 mg/L (p < 0.05) because of an increase in the nonrenal clearance. Therefore in healthy subjects, 30% of the systmic vancomycin clearance is by nonrenal mechanisms and this nonrenal clearance is concentration dependent. Assuming protein binding to be between 10% and 20%, renal vancomycin excretion is predominantly by glomerular filtration. Small amounts of tubular vancomycin transport cannot be excluded by these techniques.

This publication has 11 references indexed in Scilit: