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 [V(d)] in L/kg, half-life [T 1/4 ] in h, elimination rate constant [K(e)] in h^-1 clearance [CI] in mL/min/l.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 V(d) 0.32 ± 0.07 L/kg, t 1/4 2.32 ± 0.65 h, CI 1.7 ± 0.53 mL/min/kg, and CI 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 CI in mL/min/kg (r = 0.59), but no relationship was found between SCr and CI in mL/min/1.73 m², between age and apparent V(d)or between SCr and apparent V(d). Models for estimating CI and k(e) 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 CI and apparent V(d) 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 CIs and larger apparent V(dS) than did the older children. Dosages estimated to be necessary to achieve therapeutic concentrations were 6-8 mg/kg/d.