Population Pharmacokinetics of Teicoplanin in Preterm and Term Neonates: Is It Time for a New Dosing Regimen?
Title | Population Pharmacokinetics of Teicoplanin in Preterm and Term Neonates: Is It Time for a New Dosing Regimen? |
Publication Type | Journal Article |
Year of Publication | 2020 |
Authors | Kontou, A., Sarafidis K., Begou O., Gika H. G., Tsiligiannis A., Ogungbenro K., Dokoumetzidis A., Agakidou E., & Roilides E. |
Journal | Antimicrob Agents Chemother |
Volume | 64 |
Issue | 4 |
Date Published | 2020 03 24 |
ISSN | 1098-6596 |
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. |
DOI | 10.1128/AAC.01971-19 |
Alternate Journal | Antimicrob Agents Chemother |
PubMed ID | 31932366 |
PubMed Central ID | PMC7179285 |