Population pharmacokinetics of gentamicin in premature infants.

Abstract

The population kinetics of gentamicin were studied in 97 newborn patients with a gestational age ranging between 28 and 43 weeks and a postnatal age ranging between 2 and 30 days undergoing routine therapeutic monitoring of their serum gentamicin levels. The individual kinetic analysis of serum drug levels was performed using a single-compartment model. The clearance and apparent distribution volume were calculated in each patient. The population model employed assumes the existence of residual variability in the serum concentrations and interindividual variability in the pharmacokinetic parameters. The effects of demographic variables on the clearance, distribution volume, and optimum daily dose of gentamicin were established using multiple linear regression. Gestational age is the best predictive variable of the clearance and the optimum dose/day in the whole population studied. In the premature infant patients, the predictive capacity increases with postconceptional age. Weight is a good predictive variable of all of the parameters, especially of the apparent distribution volume in the overall population of newborns. Analysis of the population kinetic behavior and optimum dose/day in each subgroup recommends that the interval of drug administration should be increased, keeping the same dose/day ratio, due to the tendency of the drug to accumulate its long half-life, especially in premature babies.