Population Pharmacokinetics of Teicoplanin in Preterm and Term Neonates: Is It Time for a New Dosing Regimen?

Antimicrob Agents Chemother

Infectious Diseases Unit, 3rd Department of Pediatrics, Aristotle University School of Health Sciences, Hippokration General Hospital, Thessaloniki, Greece

Published: March 2020

AI Article Synopsis

  • The study aimed to create a population pharmacokinetic (PK) model to assess dosing recommendations for teicoplanin in term and preterm neonates.
  • This involved a PK study of 60 neonates, using specific loading and maintenance doses, with plasma concentrations measured by advanced chromatography techniques and analyzed using NONMEM software.
  • Findings suggested that current dosing may be inadequate for low-weight neonates, with recommendations to increase the maintenance dose for those under 2 kg to improve therapeutic outcomes.

Article Abstract

Our objective was to develop a population pharmacokinetic (PK) model in order to evaluate the currently recommended dosing regimen in term and preterm neonates. By using an optimal design approach, a prospective PK study was designed and implemented in 60 neonates with postmenstrual ages (PMA) of 26 to 43 weeks. A loading dose of 16 mg/kg was administered at day 1, followed by a maintenance dose of 8 mg/kg daily. Plasma concentrations were quantified by high-pressure liquid chromatography-mass spectrometry. Population PK (popPK) analysis was performed using NONMEM software. Monte-Carlo (MC) simulations were performed to evaluate currently recommended dosing based on a pharmacodynamic index of area under the concentration-time curve (AUC)/MIC ratio of ≥400. A two-compartment model with linear elimination best described the data by the following equations: clearance (CL) = 0.0227 × (weight [wt]/1,765) × (estimated creatinine clearance [eCRCL]/22), central compartment volume of distribution (V1) = 0.283 (wt/1,765), intercompartmental clearance () = 0.151 (wt/1,765), and peripheral compartment volume (V2) = 0.541 (wt/1,765). The interindividual variability estimates for CL, V1, and V2 were 36.5%, 45.7%, and 51.4%, respectively. Current weight (wt) and estimated creatinine clearance (eCRCL) significantly explained the observed variability. MC simulation demonstrated that, with the current dosing regimen, an AUC/MIC ratio of ≥400 was reached by only 68.5% of neonates with wt of <1 kg when the MIC was equal to 1 mg/kg, versus 82.2%, 89.7%, and 92.7% of neonates with wt of 1 to <2, 2 to <3, or ≥3 kg, respectively. Augmentation of a maintenance dose up to 10 or 11 mg/kg for preterm neonates with wt of 1 to <2 or <1 kg, respectively, increases the probability of reaching the therapeutic target; the recommended doses seem to be adequate for neonates with wt of ≥2 kg. Teicoplanin PK are variable in neonates, with wt and eCRCL having the most significant impact. Neonates with wt of <2 kg need higher doses, especially for spp. with an MIC value of ≥1 mg/liter.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179285PMC
http://dx.doi.org/10.1128/AAC.01971-19DOI Listing

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