Effect of gestational age on gentamicin pharmacokinetic parameters in the newborn

This study investigates the pharmacokinetics of gentamicin in newborns in the Special Care Nursery in University Hospital. They were divided into 3 groups according to gestational age: Group I, 26 to 30 weeks (n=10), Group II, 31 to 35 weeks (n=27), and Group III, 36 to 40 weeks (n=36). Each subject received 2.5mg/kg gentamicin (gentamicin sulphate, David Bull) every 12 h initially. The pharmacokinetic parameters for each newborn were derived from the measured plasma Cmax and Cmin,' levels taken at steady state, according to the Sawchuk-Zaske method. The subsequent dosage regimen was calculated using these parameters. Gentamicin trough levels in the newborn ranged from 0.57 to 4.94 Jig/ml. while the peak levels ranged from 4.24 to 12.42 |.Lg/1nL. The apparent volume of distribution (Vd) (means i SEM) increased with gestational age, the Va being 0.81 i 0.09, 1.00 i 0.06 and 1.49 +- 0.06 L for groups I, II and III respectively. The differences between the groups were significant (P<0.01; Student's t-test). There was an observable decrease in t} with increasing gestational age, the tm (mean i SEM) being 10.02 i 1.19 h, 8.53 i 0.38 h and 7.10 i 0.31 h for Groups I, II and III respectively. This decrease in the tm was accompanied by a similar increase in CI. (0.07 +- 0.02, 0.09 +- 0.01 and 0.15 +- 0.01 I/h for Groups I, II and III respectively). The changes int and CL were significant (P<0.01) between Groups I and III, and between Groups II and III. These findings show that differences exist in the pharrnacolcinetic parameters of newborns when grouped according to gestational age. For the effective monitoring of gentamicin especially with regard to the initial estimation of drug dosage, the appropriate set of pharmacokinetic parameters should be used for the newborn of that gestational age