W. Zhao, TINN-Global Study Group
May 17, 2019
Citations
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Influential Citations
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Citations
Quality indicators
Journal
Archives of Disease in Childhood
Abstract
Background Azlocillin is prescribed for the treatment of infections in neonatal clinical practice, however, the optimized dose is still questionable due to the lack of pharmacokinetic study Thus, we aim to evaluate the population pharmacokinetics of azlocillin and optimize dosing regimen in order to improve azlocillin treatment in neonates. Methods This is a prospective, open label pharmacokinetic study of azlocillin. Blood samples were collected using an opportunistic sampling design. Theplasma concentrations ofazlocillinwere determined by high performance liquid chromatography method with UV detection. Population pharmacokinetic-pharmacodynamic analysis was performed using NONMEM software. Results Ninety-five neonates (postmenstrual age (PMA) range 32.1–42.0 weeks) were included in this study. A total of 167 azlocillin concentrations were available for the final analysis. A one-compartment model with first-order elimination best fitted the data. Covariate analysis demonstrated that current weight, birth weight and postnatal age had significant effect on azlocillin pharmacokinetics. MonteCarlo simulation demonstrated that for the common pathogens with MIC of 8 mg/liter, the currently used dosage regimen (100 mg/kg, q12h) resulted in 61.2% of newborns achieved the pharmacodynamic target (drug concentrations above MIC during 70% of the dosing interval) with a potential risk of underdosing. When shortening the dosing interval to 8 hours, the target could be achieved in 89.3% of patients, using the MIC break point of 8 mg/liter. Conclusion The population pharmacokinetics characteristics of azlocillin were assessed in neonates. An optimal dosage regimen of azlocillin was established based on developmental pharmacokinetics-pharmacodynamics in this vulnerable population. Disclosure(s) Nothing to disclose.