Kannan Sridharan*, Muna Al Jufairi, Ali Mohamed Qader and Ola AM Elsegai Pages 1 - 11 ( 11 )
Background: Appropriate dosing of gentamicin in critically ill neonates is still debated.
Objective: To assess the peak concentration (Cmax) and area-under-the-time-concentration curve (AUC0-24 ) of gentamicin and to simulate the recommended doses using Monte Carlo method.
Methods: This was a retrospective study in critically ill neonates carried over a one-year period. The demographic characteristics, dosage regimen and gentamicin concentrations were recorded for each neonate. Using Bayesian pharmacokinetic modeling, Cmax and AUC0-24 were predicted. Dose recommendations for the target Cmax (µg/ml) of 12 was obtained, and Monte Carlo simulation (100,000 iterations) was used for predicting the pharmacokinetic parameters and recommended doses for various birth weight categories.
Results: Eighty-two critically ill neonates (with average gestational age of 33.7 weeks; and birth weight of 2.1 kg) were recruited. Higher Cmax and AUC0-24 values were predicted in premature neonates, with greater cumulative AUCs in extremely preterm neonates. The average administered dose was 4 mg/kg/day and 75% of the participants had Cmax greater than 12 µg/ml following single dose, and 85% had at steady state. On the contrary, only 25% of the study population had the recommended AUC0-24 (above 125 µg-hr/ml). Simulation tests indicate that 90% of the critically ill neonates would achieve recommended Cmax with doses ranging between 5 and 6 mg/kg/day.
Conclusion: Currently used dose of 4 mg/kg/day is adequate to maintain Cmax in large majority of the study population, with onefourth population reporting the recommended AUC0-24. Increasing the dose to 5-6 mg/kg/day more likely will help to achieve both the recommended Cmax and AUC0-24 values.
Aminoglycosides, Clinical pharmacokinetics, Gentamicin, Bayesian, Monte Carlo simulations, Dosing strategy
Department of Pharmacology & Therapeutics, Salmaniya Medical Hospital, Ministry of Health, Manama, Department of Pediatrics, College of Medicine and Medical Sciences, Arabian Gulf University, Salmaniya Medical Hospital, Ministry of Health, Manama, College of Medicine and Medical Sciences, Arabian Gulf University, Salmaniya Medical Hospital, Ministry of Health, Manama, Department of Pathology-Biochemisty, Salmaniya Medical Hospital, Ministry of Health, Manama