Population pharmacokinetics of gentamicin in South African newborns.
OBJECTIVE
Gentamicin population pharmacokinetics in newborns were studied with special reference to possible gender effects.


METHODS
Steady-state serum levels ( n=139) were obtained from 79 neonates with a mean birth weight of 2.1 kg, mean gestational age of 35.1 weeks and mean age at the time of sampling of 4.2 days. The data were analysed using the non-linear mixed effects model (NONMEM). A one-compartment model was used to fit the data.


RESULTS
The final models for clearance (CL) and volume of distribution (V) were: CL(l/h)=0.001xWGTxGAxP and V(l)=0.472xWGT, where WGT=birth weight (kg), GA=gestational age (weeks) and P=1.2 for girls and 1.0 for boys. The values of inter-individual variability in CL and V were 34% and 35%, respectively. Intra-individual variability was 5% (proportional) and 7.2% (additive). Mean (95% confidence interval) values of CL and half-life were 0.042 l h(-1) kg(-1) (0.041, 0.043 l h(-1) kg(-1)) and 8.0 h (7.7, 8.3 h), while V was 0.472 (0.428, 0.516) l/kg for all patients.


CONCLUSIONS
Mean population pharmacokinetic values were similar to those obtained with NONMEM for gentamicin in other neonates of similar age. Gender was found to be a determinant of CL, with girls clearing faster than boys.
Botha
J H
JH
Department of Experimental and Clinical Pharmacology, Nelson R. Mandela School of Medicine, Private Bag 7, 4013, Congella, South Africa. botha@nu.ac.za
du Preez
M J
MJ
Adhikari
M
M
D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics*; D001835:Body Weight; D005260:Female; D005839:Gentamicins / Q000097:blood / Q000493:pharmacokinetics*; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008657:Metabolic Clearance Rate; D017711:Nonlinear Dynamics; D012737:Sex Factors; D013019:South Africa
D000900:Anti-Bacterial Agents; D005839:Gentamicins