Renal function gentamicin

Some drugs may be less toxic in pediatric patients than in adults. Aminoglycosides appear to be less toxic in infants than in adults. In adults, aminoglycoside toxicity is related to both peripheral compartment accumulation and the individual patient s inherent sensitivity to these tissue concentrationsAlthough neonatal peripheral tissue compartments for gentamicin have been reported to closely resemble those of adults with similar renal function, gentamicin is rarely nephrotoxic in infants. This dissimilarity in the incidence of nephrotoxicity implies that newborn infants may have less inherent tissue sensitivity for toxicity than adults. 

Dosages recommended are for patients with normal renal function See Table 37-3 for appropriate dosage of gentamicin. cPediatric dose should not exceed that of a normal adult. 

Gentamicin is an aminoglycoside. All aminoglycosides tend to be nephrotoxic and ototoxic. The dose must be reduced and serum concentrations must be monitored in patients with impaired renal function. Concomitant administration of aminoglycosides and other nephrotoxic drugs, such as certain diuretics, ciclosporin, teicoplanin and vancomycin should be avoided. 

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. 

The normal half-life of aminoglycosides in serum is 2-3 hours, increasing to 24-48 hours in patients with significant impairment of renal function. Aminoglycosides are only partially and irregularly removed by hemodialysis—eg, 40-60% for gentamicin—and even less effectively by peritoneal dialysis. 

Tobramycin/Gentamicin—Patients with Normal Renal Function... 

In addition, it should be remembered that gentamicin is nephrotoxic, so that patient s renal function should be constantly monitored. If it deteriorates (i.e. the serum creatinine rises), then the patient s renal function needs to be recalculated and the dose of gentamicin amended accordingly. 

Age-related alteration of renal function is a very important factor in selecting the dose regimen. Renal function in newborns is incompletely developed. Neonatal renal plasma flow and glomerular filtration rates (normalized for body surface) are only 30-40% of those of adults. The half-life of penicillin G is 3.2 h in newborns (up to 6 days of age) and 1.4 h in infants (14 days of age or older), whereas in older children and adults, it is about 0.5 h. The mean half-life of gentamicin is about 5h in newborns under 1 week of age and about 3 h in infants 1-4 weeks of age. The half-life of gentamicin in older infants and adults is approximately 2 h. Thus, drugs that depend on renal excretion as the principal mode of elimination would be expected to have a longer residence time in infants. 

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). 

Since serum creatinine does not accurately reflect renal function in patients with spinal cord injury, dosage regimens of gentamicin should be individualized, based on age, sex, weight, height, the level of spinal cord injury, and renal function (38). 

Viotte G, Morin GP, Godin M, Fillastre JP. Chamges in the renal function of rats treated with cefoxitin and a comparison with other cephlosporinsand gentamicin. J Antimicrob Chemother 1981 7(5) 537-550... 

Aminoglycosides (24-h dosing) Gentamicin, Tobramycin, Amikacin 0.5-3 mg/L Obtain random drug level 12 h after dose After initial dose. Repeat drug level in 1 week or if renal function changes... 

Aminoglycosides are almost exclusively eliminated by glomerular filtration. Elimination is dependent on cardiovascular and renal function, age, fever, other physiological factors and the V. The half-lives are usuaUy 1-2 h in normal adult horses but are increased in horses with renal dysfunction and in neonates. Increased dosage intervals must be used in these patients to prevent nephrotoxicity. The renal elimination of the aminoglycosides increases with age. The half-life of gentamicin is approximately 50% longer in 1-day-old than in 30-day-old foals. 

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