TY - JOUR
T1 - The influence of dosage regimen on experimental gentamicin nephrotoxicity
T2 - Dissociation of peak serum levels from renal failure
AU - Bennett, William M.
AU - Plamp, Charles E.
AU - Gilbert, David N.
AU - Parker, Richard A.
AU - Porter, George A.
N1 - Funding Information:
Received for publication January 31, 1979, and in revised form April 26, 1979. This study was supported by grant no. 1 ROI OM 22928-01 from the National Institutes of Health and grant no. MRIS 0901 from the Portland Veterans Administration Hospital. Dr. Plamp was supported in part by a research fellowship from the Oregon Heart Association. Please address requests for reprints to Dr. William M. Bennett, Division of Nephrology, University of Oregon Health Sciences Center, 3181 Southwest Sam Jackson Park Road, Portland, Oregon 97201.
PY - 1979/1
Y1 - 1979/1
N2 - Peak serum levels of gentamicin were varied in rats by administering a standard nephrotoxic dosage of 40 mg/kg per day in one (QD), two, or three (TID) daily doses. The QD animals had the highest peak serum levels but showed no appreciable increase of serum creatinine concentrations over a 10-day treatment period. The TID rats had the lowest peak serum levels, but, after 10 days of drug administration, the serum creatinine concentration (2.8 ± 0.2 mg/100 ml, mean ± SE) was significantly higher than in control rats (0.6 ± 0.01 mg/100 ml) (P < 0.001). After two days of gentamicin treatment, the renal concentration of gentamicin was 269 ± 77/µ/g in the QD rats and 820 ± 29 µ/g in the TID rats (P< 0.001). In this rat model, the frequency of doses was a more important factor in the development of nephrotoxicity than the peak serum concentration of gentamicin. The results suggest that dose frequency should be considered when data from different laboratories are compared.
AB - Peak serum levels of gentamicin were varied in rats by administering a standard nephrotoxic dosage of 40 mg/kg per day in one (QD), two, or three (TID) daily doses. The QD animals had the highest peak serum levels but showed no appreciable increase of serum creatinine concentrations over a 10-day treatment period. The TID rats had the lowest peak serum levels, but, after 10 days of drug administration, the serum creatinine concentration (2.8 ± 0.2 mg/100 ml, mean ± SE) was significantly higher than in control rats (0.6 ± 0.01 mg/100 ml) (P < 0.001). After two days of gentamicin treatment, the renal concentration of gentamicin was 269 ± 77/µ/g in the QD rats and 820 ± 29 µ/g in the TID rats (P< 0.001). In this rat model, the frequency of doses was a more important factor in the development of nephrotoxicity than the peak serum concentration of gentamicin. The results suggest that dose frequency should be considered when data from different laboratories are compared.
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U2 - 10.1093/infdis/140.4.576
DO - 10.1093/infdis/140.4.576
M3 - Article
C2 - 512417
AN - SCOPUS:0018641817
SN - 0022-1899
VL - 140
SP - 576
EP - 580
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 4
ER -