Impact of small-for-gestational age (SGA) status on gentamicin pharmacokinetics in neonates

Abstract

We compared gentamicin pharmacokinetics among neonates born small-for-gestational age (SGA) and appropriate for gestational age (AGA). We further compared gentamicin pharmacokinetics in subgroups of AGA and SGA neonates born preterm and term and treated within and after the initial week of age. Steady state peak and trough serum gentamicin concentrations were used to calculate clearance (Cl), elimination constant (Kel), volume of distribution (Vd), and half-life (t1/2 ) in infants (n = 236) who received ≥48 hours therapy. Statistical analyses (SPSS 17.0) included chi-square and the non-parametric Mann-Whitney U-test. SGA infants treated early (≤7days) (n = 29) and at postmenstrual ages ≤32 weeks (n = 23) had significantly lower median Kel (0.069/h vs. 0.081/h and 0.067/h vs. 0.075/h) and clearance (0.58 mL/kg/min vs. 0.68 mL/kg/min and 0.46 mL/kg/min vs. 0.65 mL/kg/min), compared to those born AGA. There were no significant differences in pharmacokinetic profiles with later therapy or at more mature ages. The prolonged half-life of gentamicin may need to be considered in dosing regimens for preterm SGA infants in the initial week of life.

Keywords: aminoglycoside; gentamicin; pharmacokinetics; small-for gestation.