Vancomycin pharmacokinetics, renal handling, and nonrenal clearances in normal human subjects.
The renal handling of vancomycin is unknown. Previously reported studies have not achieved steady-state conditions with constant vancomycin concentrations. We measured systemic vancomycin 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 steady-state 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 para-aminohippuric 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 less than 0.05) because of an increase in the nonrenal clearance. Therefore in healthy subjects, 30% of the systemic 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.
Golper
T A
TA
Division of Nephrology and Hypertension, Oregon Health Sciences University, Portland 97201.
Noonan
H M
HM
Elzinga
L
L
Gilbert
D
D
Brummett
R
R
Anderson
J L
JL
Bennett
W M
WM
D000328:Adult; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D014640:Vancomycin / Q000493:pharmacokinetics*; D010130:p-Aminohippuric Acid / Q000493:pharmacokinetics
D014640:Vancomycin; D010130:p-Aminohippuric Acid