Elimination

The aminoglycosides are excreted almost entirely by glomerular filtration, and urine concentrations of 50-200 ^g/mL are achieved. The plasma half-lives of the aminoglycosides vary between 2 and 3 hours in patients with normal renal function.

FIGURE 45-3 Plasma concentrations (pg/mL) after administration of 5.1 mg/kg of gentamicin intravenously to a hypothetical patient either as a single dose (q24h) or as three divided doses (q8h). The threshold for toxicity has been chosen to correspond to a plasma concentration of 2 ^g/mL, the maximum recommended. The once-daily regimen produces a threefold higher plasma concentration, which enhances efficacy that otherwise might be compromised due to prolonged sub-MIC concentrations later in the dosing interval compared with the every-8-hours regimen. The once-daily regimen provides a 12-hour period during which plasma concentrations are below the threshold for toxicity, thereby minimizing the toxicity that otherwise might result from the high plasma concentrations early on. The every-8-hours regimen, in contrast, provides only a brief period during which plasma concentrations are below the threshold for toxicity.

Hours

FIGURE 45-3 Plasma concentrations (pg/mL) after administration of 5.1 mg/kg of gentamicin intravenously to a hypothetical patient either as a single dose (q24h) or as three divided doses (q8h). The threshold for toxicity has been chosen to correspond to a plasma concentration of 2 ^g/mL, the maximum recommended. The once-daily regimen produces a threefold higher plasma concentration, which enhances efficacy that otherwise might be compromised due to prolonged sub-MIC concentrations later in the dosing interval compared with the every-8-hours regimen. The once-daily regimen provides a 12-hour period during which plasma concentrations are below the threshold for toxicity, thereby minimizing the toxicity that otherwise might result from the high plasma concentrations early on. The every-8-hours regimen, in contrast, provides only a brief period during which plasma concentrations are below the threshold for toxicity.

Since aminoglycoside elimination depends almost entirely on the kidney, a linear relationship exists between the serum creatinine and the t/2 of all aminoglycosides in patients with moderately compromised renal function. Because the incidence of nephrotoxicity and ototoxicity is related to the concentration to which an aminoglycoside accumulates, it is critical to reduce the maintenance dosage of these drugs in patients with impaired renal function. The size of the individual dose, the interval between doses, or both can be altered. Determination of drug concentration in plasma is essential for the proper administration of aminoglycosides. In patients with life-threatening systemic infections, aminoglycoside concentrations should be determined several times per week (more frequently if renal function is changing) and should be determined within 24-48 hours of a change in dosage.

Aminoglycosides can be removed from the body by either hemodialysis or peritoneal dialysis. Approximately 50% of the administered dose is removed in 12 hours by hemodialysis. As a general rule, a dose equal to half the loading dose administered after each hemodialysis should maintain the plasma concentration in the desired range, but a number of variables make this a rough approximation at best. The amount of aminoglycoside removed can be replaced by administering ~15-30% of the maximum daily dose (Table 45-1) each day. Frequent monitoring of plasma drug concentrations is crucial.

Table 45-1

Algorithm for Dose Reduction of Aminoglycosides Based on Calculated Creatinine Clearance

Creatinine % of Maximum Frequency of

Clearance, mL/min Daily Dose* Dosing

Delicious Diabetic Recipes

Delicious Diabetic Recipes

This brilliant guide will teach you how to cook all those delicious recipes for people who have diabetes.

Get My Free Ebook


Post a comment