PHARMACOKINETICS OF ONCE-DAILY GENTAMICIN DOSING IN PEDIATRIC-PATIENTS

Background/Purpose: To achieve cost-effective health care in adults, o nce-daily aminoglycosides administration has been used and judged to b e safe and efficacious. A similar strategy in children requires the ch aracterization 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 bet ween 6 months and 18 years who required gentamicin therapy based on in dependent clinical assessment were eligible if they had normal renal f unction, no aminoglycoside allergies, were not neutropenic, or did not have cystic fibrosis. Measurements included a peak, 4-hour, 8-hour, a nd trough gentamicin levels to determine volume of distribution (Vd) a nd elimination constant (Ke). Ototoxicity and nephrotoxicity were moni tored by pre- and postaudiology examinations and serial calculated cre atinine 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 r uptured appendicitis (n = 19) followed by wound infections caused by t rauma (n = 4), but the spectrum of treatment was broad including enter ic, genitourinary, central nervous system, biliary, ophthalmologic, an d orthopedic infections. Pharmacokinetic data indicated that 24-hour d osing 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 nephr otoxicity or ototoxicity has been noted in either group. Conclusions: These data confirm that once-daily dosing of gentamicin is a safe meth od of treatment that provides equivalent pharmacokinetics compared wit h traditional dosing and enhances bactericidal effect based on higher peak levels, avoids toxicity, and allows cost savings. J Pediatr Surg 33:1104-1107. Copyright (C) 1998 by W.B. Saunders Company.