Gentamicin renal clearance

In renal failure changes in apparent volume of distribution do occur, and changes in a patient s hydration in particular can influence this, and therefore the renal clearance. However, the main message is that reduced renal function reduces the renal clearance of gentamicin, and this must lead to an increase in dosing interval. 

Pharmacokinetics What the patient does to the drug. For example, a patient with renal failure will have diminished renal clearance of gentamicin. 

INDOMETACIN AMINOGLYCOSIDES T amikacin, gentamicin, and vancomycin levels in neonates Uncertain indometacin possibly 1 renal clearance of these aminoglycosides Halve the dose of antibiotic. Uncertain whether this applies to adults but suggest check levels. Otherwise use an alternative NSAID... 

In the presence of Escherichia coli endotoxin-induced fever in dogs and etio-cholanolone-stimulated fever in human beings, the serum concentrations of gentamicin are lower than in the afebrile state (Fig. 3.1) (Pennington et al., 1975). This could be attributed to increased extravascular distribution of gentamicin, although renal clearance and the half-life of the antibiotic were not significantly... 

Fig. 3.1 Comparison of the mean serum gentamicin concentration-time curves in control (afebrile) and etiocholanolone-induced febrile subjects (n = 6) following the intramuscular injection of a single dose of gentamicin sulfate (1.5 mg/kg). Note the lower serum gentamicin concentrations in the presence of fever. Neither the renal clearance nor the half-life of gentamicin were significantly changed (Reproduced with permission from Pennington et al. (1975).)...

Schentag JJ, Jusko WJ. Renal clearance and tissue accumulation of gentamicin. Clin Pharmacol Ther 1977 22 364-370. 

MacDonald NE, Anas NG, Peterson RG, et al. Renal clearance of gentamicin in cystic fibrosis. J Pediatr 1983 103 985-990. 

Schentag JJ, Jusko WJ. Renal clearance and tissue accumulation of gentamicin. Clin.Pharmacol.Ther 1977 22 364-370. Gyselynck AM, Forrey A, Cutler R. Pharmacokinetics of gentamicin distribution and plasma and renal clearance. J Infect Dis... 

Renal toxicity - Renal toxicity may be characterized by decreased creatinine clearance, cells or casts in the urine, decreased urine specific gravity, oliguria, proteinuria, or evidence of nitrogen retention. Renal damage is usually reversible. The relative nephrotoxicity of these agents is estimated to be Kanamycin = Amikacin = Gentamicin = Tobramycin Streptomycin. 

A 72-year-old man was treated with ceftriaxone (2 g bd) and gentamicin (80 mg tds) for a severe urinary tract infection (75). On day 5 his serum potassium concentration was 3 mmol/1 with a normal serum creatinine and urine examination. Despite treatment with oral potassium chloride plus a high potassium diet, his serum potassium fell to 2.3 mmol/1 4 days later, accompanied by inappropriate kaliuresis, hypouricemia with inappropriate uri-cosuria, and hypophosphatemia with inappropriate phosphaturia. There was no bicarbonate wasting, but there was proteinuria 1.2 g/day, with a predominance of low molecular weight proteins in contrast, serum creatinine was normal and creatinine clearance was 78 ml/minute. The aminoglycoside was withdrawn with subsequent progressive improvement in renal proximal tubular function, which normalized 9 days later. 

Careful tailoring of the dose can prevent nephrotoxicity. In 89 critically ill patients with a creatinine clearance over 30 ml/minute who were treated with gentamicin or tobramycin 7 mg/kg/day independent of renal function, with subsequent doses chosen on the basis of the pharmacokinetics of the first dose, signs of renal impairment occurred in 14% in all survivors renal function recovered completely and hemofiltration was not needed (104). 

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