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The dissociation between aminoglycoside serum concentrations and nephrotoxicity
G Koren1, J Klein, S M MacLeod
1Dept. of Pediatrics and Pharmacology, University of Toronto.
Life Sciences
|January 1, 1988
Summary
Aminoglycoside nephrotoxicity is more severe in adult rats, even with lower drug levels. This suggests kidney damage is linked to drug accumulation, not high serum concentrations.
Area of Science:
- Pharmacology
- Toxicology
- Nephrology
Background:
- Aminoglycosides are crucial antibiotics but can cause kidney damage (nephrotoxicity).
- The relationship between drug concentration, age, and nephrotoxicity requires further clarification.
Purpose of the Study:
- To investigate the correlation between aminoglycoside dose, serum/renal concentrations, and observed nephrotoxicity in newborn versus adult rats.
- To determine if high serum concentrations or renal accumulation drives aminoglycoside-induced kidney damage.
Main Methods:
- Rats (newborn and adult) were administered aminoglycosides.
- Serum and urine creatinine, urinary N-acetylglucosaminidase and beta 2 microglobulins, and renal cortical sphingomyelinase were measured.
- Drug concentrations in serum and renal cortex were analyzed.
Main Results:
- Nephrotoxicity was significantly more pronounced in adult rats compared to newborns.
- Adult rats exhibited lower serum aminoglycoside concentrations but higher renal cortical concentrations.
- Biomarkers indicated substantial kidney damage in adults despite lower systemic drug levels.
Conclusions:
- Aminoglycoside nephrotoxicity is age-dependent, being more severe in adult rats.
- High serum aminoglycoside concentrations do not directly cause nephrotoxicity.
- Renal accumulation of aminoglycosides appears to be the primary driver of drug-associated kidney damage.