Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Mar;24(2):163-173.
doi: 10.1007/s40272-022-00493-3. Epub 2022 Mar 14.

Population Pharmacokinetics of Moxifloxacin in Children

Rachel G Greenberg  1   2 , Cornelia B Landersdorfer  3 , Nazario Rivera-Chaparro  4 , Melissa Harward  4 , Thomas Conrad  3 , Aya Nakamura  5 , Carl M Kirkpatrick  3 , Kenan Gu  6 , Varduhi Ghazaryhan  6 , Blaire Osborn  7 , Emmanuel B Walter  4   8
Affiliations

Population Pharmacokinetics of Moxifloxacin in Children

Rachel G Greenberg et al. Paediatr Drugs. 2022 Mar.

Abstract

Background/objective: Moxifloxacin is a fluoroquinolone that is commonly used in adults, but not children. Certain clinical situations compel pediatric clinicians to use moxifloxacin, despite its potential for toxicity and limited pharmacokinetics (PK) data. Our objective was to further characterize the pharmacokinetics of moxifloxacin in children.

Methods: We performed an opportunistic, open-label population PK study of moxifloxacin in children < 18 years of age who received moxifloxacin as part of standard care. A set of structural PK models and residual error models were explored using nonlinear mixed-effects modeling. Covariates with known biological relationships were investigated for their influence on PK parameters.

Results: We obtained 43 moxifloxacin concentrations from 14 participants who received moxifloxacin intravenously (n = 8) or orally (n = 6). The dose of moxifloxacin was 10 mg/kg daily in participants ≤ 40 kg and 400 mg daily in participants > 40 kg. The population mean clearance and mean volume of distribution were 18.2 L/h and 167 L, respectively. The oral absorption was described by a first-order process. The estimated extent of oral bioavailability was highly variable (range 20-91%). Total body weight was identified as a covariate on clearance and volume of distribution, and substantially reduced the random unexplained inter-individual variability for both parameters. No participants experienced suspected serious adverse reactions related to moxifloxacin.

Conclusion: These data add to the existing literature to support use of moxifloxacin in children in certain situations; however, further prospective studies on the safety and efficacy of moxifloxacin are needed.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.. Selected Diagnostic Plots
Selected diagnostic plots for the final pharmacokinetic model.
Figure 2.
Figure 2.. Simulations for Intravenous and Oral Moxifloxacin Dose
Simulations from the final model for an: A) intravenous; and B) oral dose of 400 mg and total body weight of 43 kg. Observed data shown are normalized (i.e., to a 400 mg dose and allometrically scaled to 43 kg). P10, 10th percentile of the model predictions; P50, median percentile of the model predictions; P90, 90th percentile of the model predictions
Figure 3.
Figure 3.. Probabilities of Target Attainment
Based on Monte Carlo simulations of the intravenous dosage regimens administered in the study. PK-PD targets used: fAUC/MIC ≥34 for S. pneumoniae and fAUC/MIC ≥75 for Gram-negative bacteria. fAUC/MIC, area under the free concentration-time curve in a 24-hour interval/minimum inhibitory concentration; PK-PD, pharmacokinetic-pharmacodynamic
See this image and copyright information in PMC

References

    1. DAILYMED. MOXIFLOXACIN HYDROCHLORIDE - moxifloxacin hydrochloride tablet (drug label), Mylan Pharmaceuticals Inc. Revised August 2015. DAILYMED web site. https://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid.... Accessed May 7, 2021.
    1. Burkhardt JE, Hill MA, Carlton WW, Kesterson JW. Histologic and histochemical changes in articular cartilages of immature beagle dogs dosed with difloxacin, a fluoroquinolone. Vet Pathol. 1990;27(3):162–70. doi: 10.1177/030098589002700303. - DOI - PubMed
    1. Stahlmann R, Merker HJ, Hinz N, Chahoud I, Webb J, Heger W, et al. Ofloxacin in juvenile non-human primates and rats. Arthropathia and drug plasma concentrations. Arch Toxicol. 1990;64(3):193–204. doi: 10.1007/BF02010725. - DOI - PubMed
    1. Stass H, Lettieri J, Vanevski KM, Willmann S, James LP, Sullivan JE, et al. Pharmacokinetics, safety, and tolerability of single-dose intravenous moxifloxacin in pediatric patients: dose optimization in a phase 1 study. J Clin Pharmacol. 2019;59(5):654–67. doi: 10.1002/jcph.1358. - DOI - PMC - PubMed
    1. Willmann S, Frei M, Sutter G, Coboeken K, Wendl T, Eissing T, et al. Application of physiologically-based and population pharmacokinetic modeling for dose finding and confirmation during the pediatric development of moxifloxacin. CPT Pharmacometrics Syst Pharmacol. 2019;8(9):654–63. doi: 10.1002/psp4.12446. - DOI - PMC - PubMed

LinkOut - more resources