Gentamicin elimination

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 ... 

Detailed pharmacokinetic studies were performed on transscleral iontophoresis of various drugs [38-40,42,75-78]. Each drug resulted in different patterns of distribution in the vitreous. Carboplatin distribution in the vitreous after iontophoretic delivery demonstrated heightened levels in a controlled manner from 1 to 6 h after treatment [39], Foscarnet iontophoresis demonstrated a very low elimination rate, thus therapeutic levels in the vitreous were maintained for up to 60 h [78]. Methylprednisolone obtained a relatively low peak concentration 2 h after treatment [38], and gentamicin showed a peak concentration 16 h after the transscleral iontophoresis [42]. 

FIGURE 3.6 Serum gentamicin concentrations measured in a patient during and after a 10.5-day course of therapy (80 mg every 36 hrs). Data were analyzed with the two-compartment model shown in the figure. The half-life of serum levels during therapy is primarily reflective of renal elimination. The terminal half-life seen after therapy was stopped is the actual distribution phase. (Reproduced with permission from Schentag JJ, Jusko WJ, Plant ME, Cumbo Tj, Vance JW, Abrutyn E. JAMA 1977 238 327-9.)... 

FIGURE 3.7 Decline in serum gentamicin concentrations after therapy was stopped in a patient with nephrotoxicity ( ) and a patient who did not have this adverse reaction (o). Both patients had been treated with gentamicin at an S-hour dosing interval and had nearly identical elimination-phase half-lives and peak and trough levels. (Reproduced with permission from Colburn WA, Schentag JJr Jusko WJ, Gibaldi M. J Pharmacokinet Biopharm 1978 6 179-86.)... 

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. 

Species variations in the half-life of drugs that are eliminated by renal excretion is less pronounced than for lipid-soluble drugs that undergo extensive hepatic biotransformation. The half-life of gentamicin, which is eliminated solely by glomerular filtration, is 0.5-1 h in laboratory animals, 1.25-2.5 h in domestic animals. 

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. 

In horses, 75-100% of a gentamicin dose is excreted unchanged in the urine in the first 8-24 h after administration. The half-life is 1-2 h and is longer in neonatal foals than in older foals and adult horses. Any gentamicin that accumulates in the renal cortical tissue is eliminated slowly however, these levels are often below the limits of quantification of the assays used and are, therefore, not demonstrated in pharmacokinetic studies. 

The elimination of amikacin is similar to gentamicin. The half-life of amikacin ranges from 1 to 3 h in adult horses but may be as long as 5 h in neonatal foals. 

Following parenteral administration, the distribution of gentamicin is virtually restricted to extracellular fluid, and elimination takes place solely by glomerular filtration. The pattern of age-related changes in the disposition of gentamicin is similar in foals (Cummings et al.r 1990) and in calves (Clarke et al.r 1985). Values of the systemic clearance of gentamicin in 1- and 5-day-old foals and calves compared with mares and cows, respectively, indicate that... 

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