Gentamicin and tobramycin pharmacokinetics in pediatric bone marrow transplant patients

To describe the pharmacokinetic parameters of gentamicin and tobramycin in pediatric bone marrow transplant patients.

Retrospective medical record review.

Pediatric bone marrow transplant unit in a university teaching hospital.

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.

Thirty-three patients aged 15 years or less who underwent bone marrow transplant and received gentamicin or tobramycin.

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.

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.