Gentamicin clearance

Ernest D, Cutler DJ. Gentamicin clearance during continuous arteriovenous hemodiafiltration. Crit Care Med 1992 20 586-9. 

A study found that amikacin or gentamicin clearance was impaired in 12 of 17 children given amphotericin B. Serum creatinine increased by 50% or more in 3 of them, but there was no significant increase in creatinine levels in 7 others. As a result, the aminoglycoside dose was decreased or the dose interval lengthened in 7 children. ... 

Cisplatin is nephrotoxic and it would appear that its damaging effects on the kidney are additive with the nephrotoxic effects of the aminoglycoside antibacterials. Both gentamicin and cisplatin may cause ototoxicity. Previous exposure to cisplatin caused a significant decrease in gentamicin clearance in rats. 

Penicillin or ceftriaxone together with gentamicin has not demonstrated superior cure rates compared with monotherapy with penicillin or ceftriaxone for patients with highly susceptible strain gentamicin therapy should not be administered to patients with creatinine clearance of less than 30 mL/min... 

Gentamicin is shown to have a Vd of 0.25 L per kg of the body weight. If the weight of the patient is 132 lb, and the elimination rate constant is 0.33 hour 1, what is the total clearance of gentamicin ... 

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. 

In fact elderly people have a reduced creatinine clearance, often balanced by the decline in creatinine input with a resulting normal serum creatinine. This is clinically important because drugs which are cleared through the kidneys need to be given in scaled down amounts to prevent cumulation and possible toxicity - e.g., gentamicin and other parenteral aminoglycosides, digoxin. 

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. 

Bioadhesive microspheies composed from a variety of materials such as starch, carbomer, hyaluronan esters, dextrans have been used to prolong the retention time of the drug within the nasal cavity. The clearance half-life of microspheies can be in the order of 3-4 hours, in comparison with 15 minutes for a simple solution. Improved bioavailabilities have been seen for gentamicin, insulin and desmopressin. 

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... 

FIGURE 23.7 Plasma clearance of gentamicin in premature (<37-week gestation, solid bars) and full-term (open bars) newborns at various postnatal ages. (Data from Pons G et al. Ther Drug Monit 1988 10 42-7.)... 

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