The effect of tobramycin on the renal handling of vancomycin.
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.
Munar
M Y
MY
College of Pharmacy, Oregon State University, Department of Medicine, Portland 97201-3098.
Elzinga
L
L
Brummett
R
R
Golper
T A
TA
Bennett
W M
WM
D000328:Adult; D001299:Audiometry; D003404:Creatinine / Q000378:metabolism; D004338:Drug Combinations; D004347:Drug Interactions; D005260:Female; D006311:Hearing Disorders / Q000139:chemically induced; D006801:Humans; D007444:Inulin / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D014031:Tobramycin / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D014640:Vancomycin / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D010130:p-Aminohippuric Acid / Q000378:metabolism
D004338:Drug Combinations; D014640:Vancomycin; D007444:Inulin; D003404:Creatinine; D014031:Tobramycin; D010130:p-Aminohippuric Acid