Multiexponential elimination of gentamicin. A kinetic study during development

The long-term disposition of gentamicin (up to 100-240 h) was studied in 13 premature newborns (33 weeks mean gestational age) and in 7 infants and children (1 month to 8 years). The data fitted bi- or triexponential curves with terminal half-lives averaging 51 and 37 h. Newborns showed lower values of body clearance, central compartment and steady state volumes of distribution than infants and children (respectively, 12.8 vs. 50.4 ml/min/1.73 m², 9.03 vs. 17.5 liters/1.73 m², and 15.7 vs. 35.5 liters/1.73 m²). The ratio between the amount of gentamicin predicted at steady state in the tissue compartment and in the total body was also significantly lower in newborns than in the older group (0.4 vs. 0.52). These data provide pharmacokinetic demonstration of an age dependence in gentamicin tissue distribution and excretion during the early stages of human development.