Gentamicin and tobramycin pharmacokinetics in pediatric bone marrow transplant patients

OBJECTIVE: To describe the pharmacokinetic parameters of gentamicin and tobramycin in pediatric bone marrow transplant patients. DESIGN: Retrospective medical record review. SETTING: Pediatric bone marrow transplant unit in a university teaching hospital. MAIN OUTCOME MEASURES: Pharmacokinetic parameters (apparent volume of distribution [Vd] in L/kg, half-life [t1/2] in h, elimination rate constant [ke] in h-1, clearance [Cl] in mL/min/1.73 m2 and mL/min/kg) calculated from serum concentrations. PATIENTS: Thirty-three patients aged 15 years or less who underwent bone marrow transplant and received gentamicin or tobramycin. RESULTS: Mean pharmacokinetic parameters were Vd 0.32 +/- 0.07 L/kg, t1/2 2.32 +/- 0.65 h, Cl 1.71 +/- 0.53 mL/min/kg, and Cl 86.2 +/- 24.5 mL/min/1.73 m2. Factors such as disease state, type of marrow graft, gender, or exposure to cyclosporine had no significant effect on pharmacokinetic parameters. Linear regression indicated a weak relationship between serum creatinine (SCr) and Cl in mL/min/kg (r = 0.59), but no relationship was found between SCr and Cl in mL/min/1.73 m2, between age and apparent Vd, or between SCr and apparent Vd. Models for estimating Cl and Ke developed by multiple regression were somewhat predictive (r = 0.7). Required calculated maintenance dosages to obtain therapeutic concentrations were 8, 7, and 6 mg/kg/d in children 6 or younger, 7-12, and 13-15 years, respectively. CONCLUSIONS: The mean Cl and apparent Vd for all ages are similar to those reported in pediatric oncology patients who had not undergone marrow transplantation. Children 6 years or younger had lower than expected Cls and larger apparent Vds than did the older children. Dosages estimated to be necessary to achieve therapeutic concentrations were 6-8 mg/kg/d.

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