Pharmacokinetic basis for the use of extended interval dosage regimens of gentamicin in neonates

• Published in: Journal of antimicrobial chemotherapy Vol. 54; no. 1; pp. 193 - 198
• Main Authors: Lanao, José M., Calvo, Mª Victoria, Mesa, José Antonio, Martín-Suárez, Ana, Carbajosa, Mª Teresa, Miguelez, Francisco, Domínguez-Gil, Alfonso
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-07-2004; Oxford Publishing Limited (England)
• Subjects: Algorithms; aminoglycosides; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - pharmacokinetics; Antibiotics. Antiinfectious agents. Antiparasitic agents; Bayes Theorem; Biological and medical sciences; Birth Weight; extended-interval dosage regimens; Gentamicins - administration & dosage; Gentamicins - pharmacokinetics; Gram-Negative Bacterial Infections - drug therapy; Gram-Negative Bacterial Infections - metabolism; Half-Life; Humans; Infant, Newborn; Infant, Premature; Medical sciences; Models, Biological; Pharmacology. Drug treatments; Population; population pharmacokinetics; Reproducibility of Results; Retrospective Studies; Human; Antibiotic; Newborn; Aminoglycoside; Gentamicin; Use; Antibacterial agent; Pharmacokinetics
• ISSN: 0305-7453; 1460-2091; 1460-2091
• DOI: 10.1093/jac/dkh261

Objectives: To analyse the pharmacokinetic basis for the use of extended-interval dosage regimens of gentamicin in neonates using population pharmacokinetics. Patients and 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 × W (kg)0.852; clearance, Cl (L/h)=0.032 × W (kg)1.482+0.0024 × 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.