Gentamicin dosage in children: A randomized prospective comparison of body weight and body surface area as dose determinants

Evans, William E.; Feldman, Sandor; Ossi, Michael; Taylor, Robert H; Chaudhary, Subhash; Melton, Emily T.; Barker, Larry F.

doi:10.1016/s0022-3476(79)80380-7

Cited by 13 publications

(9 citation statements)

References 10 publications

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“…The values of these parameters with and without the correction of first-dose half-lives by Evans' method (Evans et aI., 1980) are presented in table III. The mean value and distribution of these parameters are nearly identical to values reported by others from similar studies in subjects in this age range (Evans et al, 1979(Evans et al, , 1980. A subset of 'reliable' kinetic studies was examined to determine whether anomalous results (from studies which were subsequently found not to represent disposition of the drug in that patient) had skewed the population parameters.…”

Section: Tobramycin Pharmacokineticssupporting

confidence: 88%

Tobramycin Serum Level Monitoring in Young Patients with Normal Renal Function

Green

Mirkin

Peterson

et al. 1984

Clinical Pharmacokinetics

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Five clinical strategies for monitoring serum tobramycin concentrations were compared in a population of children and young adults with normal renal function receiving tobramycin for suspected sepsis. The drug monitoring strategies were evaluated on the basis of the ability of each to predict subsequent drug levels. The strategies included 3 methods requiring assessment of individual drug disposition: (a) measurement of peak drug concentrations after 2 separate doses; (b) a 3-point kinetic study to define distribution volume and elimination rate; (c) a 3-point kinetic study with adjustment of the value for elimination rate to account for deep compartment drug accumulation; and 2 strategies using a fixed-dose approach in which prediction of individual levels was made on the basis of mean population kinetic parameters. Although all methods were of similar accuracy, the fixed-dose strategy was the most precise in predicting subsequent serum tobramycin levels (95% tolerance limits = 84-135% of predicted). Poor performance of the other strategies was accounted for by interpatient variability of tobramycin disposition that was small relative to the intrapatient variability in these measurements. We conclude that these strategies for aminoglycoside serum level monitoring, which have proven beneficial in patients with impaired renal function, afford little benefit to children and young adults with normal renal function. Administration of these drugs on a fixed-dose schedule without serum concentration monitoring appears to be warranted in this select population. Alternatively, specific strategies for this population must be developed that consider the small interindividual differences in drug disposition and low incidence of toxicity.

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Section: Tobramycin Pharmacokineticssupporting

confidence: 88%

Tobramycin Serum Level Monitoring in Young Patients with Normal Renal Function

Green

Mirkin

Peterson

et al. 1984

Clinical Pharmacokinetics

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“…Our data provide further information on gentamicin disposition with significant differences from the results of previous studies (5,7,15,17,18,22), which followed washout of the aminoglycoside for briefer periods of time and thus incompletely characterized this age group. As occurs in the adult, long-term blood sampling after cessation of treatment revealed marked retention of gentamicin in the body of infants.…”

Section: Discussioncontrasting

confidence: 84%

Multiexponential Elimination of Gentamicin

Bm¹,

Cavanna²,

Wj³

et al. 1980

Dev Pharmacol Ther

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The long-term disposition of gentamicin (up to 100-240 h) was studied in 13 premature newborns (33 weeks mean gestational age) and in 7 infants and children (1 month to 8 years). The data fitted bi- or triexponential curves with terminal half-lives averaging 51 and 37 h. Newborns showed lower values of body clearance, central compartment and steady state volumes of distribution than infants and children (respectively, 12.8 vs. 50.4 ml/min/1.73 m^2, 9.03 vs. 17.5 liters/l.73 m^2, and 15.7 vs. 35.5 liters/l.73 m^2). The ratio between the amount of gentamicin predicted at steady state in the tissue compartment and in the total body was also significantly lower in newborns than in the older group (0.4 vs. 0.52). These data provide pharmacokinetic demonstration of an age dependence in gentamicin tissue distribution and excretion during the early stages of human development.

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“…The peak levels had virtually no relationship to surface area, as might have been predicted from the lack of correlation between Vd and surface area. This is consistent with recent data on gentamicin suggesting that the variability in serum concentrations is not improved by calculating doses on the basis of surface area (7).…”

supporting

confidence: 92%

“…Our study of the pharmacokinetics of amikacin on children agrees with other reports evaluating gentamicin and tobramycin in concluding that the recommended dosage schedule for children is different from that for adults (7,10). Since the pharmacokinetic parameters of these drugs are different in children, recommended dosage schedules should be based upon evaluation in pediatric patients rather than extrapolation from data from studies in adult patients.…”

supporting

confidence: 85%

Amikacin pharmacokinetics in pediatric patients with malignancy

Cleary¹,

Pickering²,

Kramer³

et al. 1979

Antimicrob Agents Chemother

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The pharmacokinetics of anmikacin were evaluated in 50 pediatric patients (1 to 17 years of age) with malignancies and nonnal renal function. Dosage regimens of 5 mg/kg per dose were administered intravenously (i) over 30 min every 8 h, (ii) over 60 min every 8 h, and (iii) over 60 min every 6 h. Administration of amikacin over 30 mim produced concentrations in serum of 29.3 ± 5.7 jig/ml at the end of the infusion and subtherapeutic concentrations 4 h after the infusion. The regimen of 20 mg/kg per 24 h, divided into doses given every 6 h infused over 60 min, achieved concentrations in serum at the end of the infusion of 17.2 ± 1.7 jsg/ml and at 6 h of 1.2 ± 0.3 ,ug/ml. The serum half-life was 1.24 ± 0.09 h, volume of distribution was 0.26 ± 0.02 liter/kg, and total body clearance rate was 131 ± 10 ml/min per 1.73 m2. No accumulation of amnikacin was noted, and no significant side effects could be attributed to the drug. This study suggests that the optimal initial dosage regimen of amikacin in children is 20 mg/kg per 24 h administered in equal doses every 6 h over 60 min; however, optimal therapy requires individualization of dosage based on measured serum concentrations and susceptibility data on bacterial pathogens isolated.

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Gentamicin dosage in children: A randomized prospective comparison of body weight and body surface area as dose determinants

Cited by 13 publications

References 10 publications

Tobramycin Serum Level Monitoring in Young Patients with Normal Renal Function

Tobramycin Serum Level Monitoring in Young Patients with Normal Renal Function

Multiexponential Elimination of Gentamicin

Amikacin pharmacokinetics in pediatric patients with malignancy

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