Pharmacokinetic basis for the use of extended interval dosage regimens of gentamicin in neonates.
OBJECTIVE
To analyse the pharmacokinetic basis for the use of extended-interval dosage regimens of gentamicin in neonates using population pharmacokinetics.


METHODS
The population pharmacokinetics of gentamicin was studied retrospectively in a population of 113 neonates divided into two groups: one for computing the population model (n=97) and another for validation (n=36). A one-compartment pharmacokinetic model and non-linear mixed-effects modelling were used to assess the population pharmacokinetic model.


RESULTS
Weight (W) and postnatal age (PA) were the covariates that influenced the pharmacokinetic parameters of gentamicin. The final population model obtained was: distribution volume, V (L)=0.636 x W (kg)0.852; clearance, Cl (L/h)=0.032 x W (kg)1.482+0.0024 x PA (days). The predictive performance of the model in the population validation was adequate for clinical purposes. The optimized population model allowed us to simulate gentamicin serum levels and their variability, in this kind of patient, when extended-interval dosage administration regimens were implemented.


CONCLUSIONS
According to our pharmacokinetic population model, initial doses of gentamicin of 10 mg/kg, and dosage intervals between 36-48 h, appear to be appropriate to achieve target peak and trough serum levels of 15-20 and <0.5 mg/L, respectively, when extended-interval dosage regimens are implemented in newborns. The half-life of gentamicin in premature babies of very low weight and gestational age <31 weeks is long. Thus, to achieve serum concentrations in the 1-10 mg/L range, the use of dosage regimens of 5 mg/kg at 36-48 h dosage intervals seems suitable.
Lanao
José M
JM
Departments of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, and University Hospital, University of Salamanca, Salamanca, Spain. jmlanao@usal.es
Calvo
Maria Victoria
MV
Mesa
José Antonio
JA
Martín-Suárez
Ana
A
Carbajosa
Maria Teresa
MT
Miguelez
Francisco
F
Domínguez-Gil
Alfonso
A
D000465:Algorithms; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001499:Bayes Theorem; D001724:Birth Weight; D005839:Gentamicins / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D008954:Models, Biological; D011153:Population; D015203:Reproducibility of Results; D012189:Retrospective Studies
D000900:Anti-Bacterial Agents; D005839:Gentamicins