Effects of Hydration on Gentamicin Excretion and Renal Accumulation in Furosemide-Treated Rats

Chiu, Peter; Long, James F.

doi:10.1128/aac.14.2.214

Cited by 35 publications

(11 citation statements)

References 10 publications

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“…Sodium depletion has been shown to increase nephrotoxicity (2). When Chiu and Long controlled for water losses in rats, they failed to find that furosemide increased gentamicin nephrotoxicity (7). Our data are consistent with these observations and suggest that furosemide can be given to patients receiving aminoglycosides without increased risk of nephrotoxicity.…”

Section: Methodssupporting

confidence: 81%

Effect of furosemide on aminoglycoside-induced nephrotoxicity and auditory toxicity in humans

Smith

Lietman²

1983

Antimicrob Agents Chemother

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Section: Methodssupporting

confidence: 81%

Effect of furosemide on aminoglycoside-induced nephrotoxicity and auditory toxicity in humans

Smith

Lietman²

1983

Antimicrob Agents Chemother

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“…Aronoff et al (1) and Bennett et al (3) suggested that the deterioration in renal function is related to the degree of drug accumulation in the kidney. Others provided evidence contrary to this (6,11,17,19). It is evident that this question has yet to be answered, but our results support a relationship between renal uptake of drugs and change in renal function.…”

Section: Resultssupporting

confidence: 59%

Role of sodium in protection by extended-spectrum penicillins against tobramycin-induced nephrotoxicity

Sabra

Branch

1990

Antimicrob Agents Chemother

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Salt depletion is known to potentiate aminoglycoside nephrotoxicity, while salt replacement attenuates it.Recent studies have shown that ticarcillin protects against tobramycin and gentamicin nephrotoxicity. It has been suggested that this protection is due to an interaction between ticarcillin and the aminoglycoside. However, it can also be explained by the salt load associated with ticarcillin administration. This study was conducted to examine this question. Tobramycin was administered to eight groups of rats at 100 mg/kg per day intraperitoneally for 10 days. Group 1 rats were salt depleted, while group 2 rats were on a normal salt diet. Rats in groups 3 through 8 were also salt depleted but received, in addition, the following interventions intraperitoneally: group 3, ticarcillin, 300 mg/kg per day (0.37 to 0.39 meq of Na supplement per day); group 4, ticarcillin, 300 mg per day (1.56 meq of Na supplement per day); group 5, ticarcillin, 300 mg/kg per day, and NaCl supplement (1.17 to 1.19 meq/day), resulting in a total load of 1.56 meq/day; group 6, piperacillin, 400 mg/day (0.76 meq of Na supplement per day and equimolar to the ticarcillin dose [300 mg/day] in group 4 rats); group 7, piperacillin, 400 mg/day, and NaCI supplement (0.8 meq/day) for a total Na load of 1.56 meq/ day; and group 8, 1.56 meq of Na per day as NaCl. Rats in groups 2, 4, 5, 7, and 8, which received a normal salt diet or its equivalent Na supplement, had no significant change in creatinine clearance (CLCR) over the 10-day period. The remaining groups sustained significant reductions in CLCR, as follows: group 1, -53.0% (P < 0.05); group 3, -66.2% (P < 0.05); group 6, -79.8% (P < 0.05). A positive correlation was found between the concentration of tobramycin in the kidneys and the percent change in CLCR at the end of the study.Concentrations of drug in plasma were highest in group 1 rats, lowest in the rats in groups in which protection was observed, and moderately elevated in the remaining groups of rats. The results of this study suggest the following: (i) that the protective effect of ticarcillin against tobramycin nephrotoxicity is secondary to the obligatory sodium load associated with it, (ii) pharmacokinetic and pharmacodynamic interactions between salt and tobramycin are proposed to explain this effect, (iii) the nephrotoxicity of tobramycin is probably related to the degree of accumulation of the drug in the kidney, and (iv) an in vivo interaction between tobramycin and ticarcillin does not contribute to the protective effect of the penicillin but may influence concentrations in plasma, especially under conditions of severe renal impairment.Aminoglycosides (AGSs) are frequently used for the treatment of gram-negative bacterial infections, usually in combination with extended-spectrum penicillins, to provide synergistic antipseudomonal activity. One of the major limiting factors in their use is the development of nephrotoxicity, which remains a problem, despite close monitoring of plasma drug levels in patients. Several factor...

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“…Factors reported to enhance gentamicin nephrotoxicity include dehydration (13). sodium (8), or potassium (I I) depletion; acidosis (21); diuretic administration (I); and concomitant use of cephalosporins (9).…”

Section: Discussionmentioning

confidence: 99%

Pathophysiologic Evidence of Gentamicin Nephrotoxicity in Neonatal Puppies

1980

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SummaryNewborn puppies were paired (n = 21 pairs) at birth, given gentamicin (5 mg/kg/day for 7 days and then 7.5 mg/kg/day) or saline intramuscularly (IM) and studied at 10, 20, or 30 days of age. Peak gentamicin concentrations correlated neither with total body water nor extracellular fluid volume. The ratio of outer/inner cortical gentamicin concentrations increased with therapy (n = 0.579; P < 0.01). Pathologic changes in proximal tubular cells of superficial and juxtamedullary cortices corresponded to tissue accumulation of gentamicin. Inulin clearance was lower but not statistically different in gentamicin puppies at 20 and 30 days, but tubular reabsorption of phosphate was lower at 30 davs ( P < 0.02).Plasma creatinine decreased during the first month of fife in both control and gentamicin puppies (n = -0.370; P < 0.02) and was not different between puppies even at 20 and 30 days when tubular damage was marked. No differences in urine sediment, osmolarity, glucose, and protein concentrations were noted between paired animals. Mean values of gentamicin half-life in gentamicin (control) puppies decreased from 80.3 (84.0) min at 10 days to 45.3 (50.3) min a t 20 days, but increased to 61.0 (40.0; P < 0.05) min at 30 days. Similar studies in older puppies and adult animals given gentamicin resulted in an increase in plasma creatinine and gentamicin half-life within 10 days.

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Effects of Hydration on Gentamicin Excretion and Renal Accumulation in Furosemide-Treated Rats

Cited by 35 publications

References 10 publications

Effect of furosemide on aminoglycoside-induced nephrotoxicity and auditory toxicity in humans

Effect of furosemide on aminoglycoside-induced nephrotoxicity and auditory toxicity in humans

Role of sodium in protection by extended-spectrum penicillins against tobramycin-induced nephrotoxicity

Pathophysiologic Evidence of Gentamicin Nephrotoxicity in Neonatal Puppies

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