Pharmacokinetics of once-daily gentamicin dosing in pediatric patients.
OBJECTIVE
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.
Children's Hospital, Denver, Colorado 80218, USA.
K D
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Bass
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Larkin
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Paap
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Haase
D000293:Adolescent; D000704:Analysis of Variance; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000191:economics / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D017046:Cost Savings; D003404:Creatinine / Q000097:blood; D016903:Drug Monitoring / Q000191:economics; D005260:Female; D005839:Gentamicins / Q000008:administration & dosage / Q000191:economics / Q000493:pharmacokinetics*; D006801:Humans; D007223:Infant; D008297:Male; D011446:Prospective Studies
D000900:Anti-Bacterial Agents; D005839:Gentamicins; D003404:Creatinine