Pharmacokinetics of once-daily gentamicin dosing in pediatric patients
Background/Purpose: To achieve cost-effective health care in adults, once-daily aminoglycosides administration has been used and judged to be safe and efficacious. A similar strategy in children requires the characterization of pharmacokinetic parameters and the development of a therapeutic monitori...
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Published in | Journal of pediatric surgery Vol. 33; no. 7; pp. 1104 - 1107 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
01.07.1998
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Subjects | |
Online Access | Get full text |
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Summary: | Background/Purpose:
To achieve cost-effective health care in adults, once-daily aminoglycosides administration has been used and judged to be safe and efficacious. A similar strategy in children requires the characterization of pharmacokinetic parameters and the development of a therapeutic monitoring protocol for this antibiotic regimen.
Methods:
A prospective, controlled, randomized (2:1) study was undertaken in 50 pediatric patients between June 1995 and September 1997. Children between 6 months and 18 years who required gentamicin therapy based on independent clinical assessment were eligible if they had normal renal function, no aminoglycoside allergies, were not neutropenic, or did not have cystic fibrosis. Measurements included a peak, 4-hour, 8-hour, and trough gentamicin levels to determine volume of distribution (Vd) and elimination constant (Ke). Ototoxicity and nephrotoxicity were monitored by pre- and postaudiology examinations and serial calculated creatinine clearance determinations, respectively.
Results:
Thirty-three patients received 7.5 mg/kg every 24 hours, and 17 patients received 2.5 mg/kg every 8 hours. Most frequent indications for treatment were ruptured appendicitis (n = 19) followed by wound infections caused by trauma (n = 4), but the spectrum of treatment was broad including enteric, genitourinary, central nervous system, biliary, ophthalmologic, and orthopedic infections. Pharmacokinetic data indicated that 24-hour dosing resulted in higher peak levels compared with 8-hour dosing (20.4 ± 45.4
v 7.2 ± 6.2 mg/L,
P<.0001) and lower trough levels (0.29 ± .02
v 0.69 ± 0.13,
P<.0001), whereas rate of elimination constant and volume of distribution were not significantly different. No nephrotoxicity or ototoxicity has been noted in either group.
Conclusions:
These data confirm that once-daily dosing of gentamicin is a safe method of treatment that provides equivalent pharmacokinetics compared with traditional dosing and enhances bactericidal effect based on higher peak levels, avoids toxicity, and allows cost savings. |
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ISSN: | 0022-3468 1531-5037 |
DOI: | 10.1016/S0022-3468(98)90540-1 |