The Effect of Tobramycin on the Renal Handling of Vancomycin

Abstract

Studies in experimental animals and humans have suggested that enhanced renal and auditory toxicity occur with concurrent vancomycin and aminoglycoside treatment. In volunteers, systemic vancomycin clearance at steady-state was measured simultaneously with renal clearances of vancomycin, creatinine, inulin, and para-aminohippurate. Group 1 (n = 9) received vancomycin 5 mg/kg IV for 1 hour, then 1.1 mg/kg/hr for 3 hours. Group II (n = 7) received vancomycin plus tobramycin (2 mg/kg IV over 30 min). Groups did not differ demographically. Audiograms were obtained before and after vancomycin. Plasma samples were collected serially for vancomycin and tobramycin pharmacokinetic studies. Serum concentration versus time data were fit to a two-compartment model for vancomycin and a one-compartment model for tobramycin. For all volunteers, creatinine, inulin and para-aminohippurate clearance, and audiograms were not altered from baseline and were not statistically different between groups. No significant effect of tobramycin on vancomycin pharmacokinetics was observed. conversely, vancomycin had no significant effect on tobramycin pharmacokinetics. The nephrotoxic synergism of vancomycin and tobramycin is not explained by short-term differences in renal handling.

Evaluation of the Risk for Acute Kidney Injury in Adult Cystic Fibrosis Patients Receiving Concomitant Vancomycin and Tobramycin

“…Although bound to the same cellular organelle, neither vancomycin nor tobramycin has been shown to cause a disruption in the pharmacokinetics of the other antimicrobial when both medications are used together. Evidence suggests their subcellular distributions are different and thus they are metabolized differently by the cell [ 22 , 23 ].…”

Vancomycin Trough Levels: Cause or Result of Acute Kidney Injury?

“…It has been difficult to produce vancomycin nephrotoxicity in experimental animals over the past years although there seems to be a synergistic nephrotoxic effect when combined with aminoglycoside [3,6] . The instance of nephrotoxicity defined differently by various authors has been estimated to be approximately 5% [4] .…”