Rachel G Greenberg1,2, Cornelia B Landersdorfer3, Nazario Rivera-Chaparro4, Melissa Harward4, Thomas Conrad3, Aya Nakamura5, Carl M Kirkpatrick3, Kenan Gu6, Varduhi Ghazaryhan6, Blaire Osborn7, Emmanuel B Walter4,8. 1. Duke Clinical Research Institute, Duke University School of Medicine, 300 W. Morgan St, Durham, NC, 27701, USA. rachel.greenberg@duke.edu. 2. Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA. rachel.greenberg@duke.edu. 3. Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia. 4. Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA. 5. The Emmes Company, LLC, Rockville, MD, USA. 6. Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. 7. Office of Clinical Pharmacology, United States Food and Drug Administration, Silver Spring, MD, USA. 8. Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
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.
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.
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