The english version of the website is under development. Wherever text appears in Greek, it means it has not been translated yet.

Δημοσίευση

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

TitlePopulation Pharmacokinetics of Teicoplanin in Preterm and Term Neonates: Is It Time for a New Dosing Regimen?
Publication TypeJournal Article
Year of Publication2020
AuthorsKontou, A., Sarafidis K., Begou O., Gika H. G., Tsiligiannis A., Ogungbenro K., Dokoumetzidis A., Agakidou E., & Roilides E.
JournalAntimicrob Agents Chemother
Volume64
Issue4
Date Published2020 03 24
ISSN1098-6596
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.

DOI10.1128/AAC.01971-19
Alternate JournalAntimicrob Agents Chemother
PubMed ID31932366
PubMed Central IDPMC7179285

Contact

Secretariat of the School of Medicine
 

Connect

School of Medicine's presence in social networks
Follow Us or Connect with us.