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Pharmacokinetics and Dosing of Levofloxacin in Children Treated for Active or Latent Multidrug-resistant Tuberculosis, Federated States of Micronesia and Republic of the Marshall Islands.

Publication ,  Journal Article
Mase, SR; Jereb, JA; Gonzalez, D; Martin, F; Daley, CL; Fred, D; Loeffler, AM; Menon, LR; Bamrah Morris, S; Brostrom, R; Chorba, T; Peloquin, CA
Published in: Pediatr Infect Dis J
April 2016

BACKGROUND: In the Federated States of Micronesia and then the Republic of the Marshall Islands (RMI), levofloxacin pharmacokinetics were studied in children receiving directly observed once-daily regimens (10 mg/kg, age >5 years; 15-20 mg/kg, age ≤5 years) for either multidrug-resistant tuberculosis disease or latent infection after multidrug-resistant tuberculosis exposure, to inform future dosing strategies. METHODS: Blood samples were collected at 0 (RMI only), 1, 2 and 6 hours (50 children, aged 6 months to 15 years) after oral levofloxacin at >6 weeks of treatment. Clinical characteristics and maximal drug concentration (Cmax) of levofloxacin, elimination half-life and area under the curve from 0 to 24 hours (AUC0-24 hours × μg/mL) were correlated to determine the optimal dosage and to examine associations. Population pharmacokinetics and target attainment were modeled. With results from the Federated States of Micronesia, dosages were increased in RMI toward the target Cmax for Mycobacterium tuberculosis, 8-12 µg/mL. RESULTS: Cmax correlated linearly with per-weight dosage. Neither Cmax nor half-life was associated with gender, age, body mass index, concurrent medications or predose meals. At levofloxacin dosage of 15-20 mg/kg, Cmax ≥8 µg/mL was observed, and modeling corroborated a high target attainment across the ratio of the area under the free concentration versus time curve to minimum inhibitory concentration (fAUCss,0-24/MIC) values. CONCLUSIONS: Levofloxacin dosage should be 15-20 mg/kg for Cmax ≥8 µg/mL and a high target attainment across fAUCss,0-24/MIC values in children ≥2 years of age.

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Published In

Pediatr Infect Dis J

DOI

EISSN

1532-0987

Publication Date

April 2016

Volume

35

Issue

4

Start / End Page

414 / 421

Location

United States

Related Subject Headings

  • Tuberculosis, Multidrug-Resistant
  • Pediatrics
  • Mycobacterium tuberculosis
  • Micronesia
  • Microbial Sensitivity Tests
  • Male
  • Levofloxacin
  • Latent Tuberculosis
  • Infant
  • Humans
 

Citation

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ICMJE
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Mase, S. R., Jereb, J. A., Gonzalez, D., Martin, F., Daley, C. L., Fred, D., … Peloquin, C. A. (2016). Pharmacokinetics and Dosing of Levofloxacin in Children Treated for Active or Latent Multidrug-resistant Tuberculosis, Federated States of Micronesia and Republic of the Marshall Islands. Pediatr Infect Dis J, 35(4), 414–421. https://doi.org/10.1097/INF.0000000000001022
Mase, Sundari R., John A. Jereb, Daniel Gonzalez, Fatma Martin, Charles L. Daley, Dorina Fred, Ann M. Loeffler, et al. “Pharmacokinetics and Dosing of Levofloxacin in Children Treated for Active or Latent Multidrug-resistant Tuberculosis, Federated States of Micronesia and Republic of the Marshall Islands.Pediatr Infect Dis J 35, no. 4 (April 2016): 414–21. https://doi.org/10.1097/INF.0000000000001022.
Mase, Sundari R., et al. “Pharmacokinetics and Dosing of Levofloxacin in Children Treated for Active or Latent Multidrug-resistant Tuberculosis, Federated States of Micronesia and Republic of the Marshall Islands.Pediatr Infect Dis J, vol. 35, no. 4, Apr. 2016, pp. 414–21. Pubmed, doi:10.1097/INF.0000000000001022.
Mase SR, Jereb JA, Gonzalez D, Martin F, Daley CL, Fred D, Loeffler AM, Menon LR, Bamrah Morris S, Brostrom R, Chorba T, Peloquin CA. Pharmacokinetics and Dosing of Levofloxacin in Children Treated for Active or Latent Multidrug-resistant Tuberculosis, Federated States of Micronesia and Republic of the Marshall Islands. Pediatr Infect Dis J. 2016 Apr;35(4):414–421.

Published In

Pediatr Infect Dis J

DOI

EISSN

1532-0987

Publication Date

April 2016

Volume

35

Issue

4

Start / End Page

414 / 421

Location

United States

Related Subject Headings

  • Tuberculosis, Multidrug-Resistant
  • Pediatrics
  • Mycobacterium tuberculosis
  • Micronesia
  • Microbial Sensitivity Tests
  • Male
  • Levofloxacin
  • Latent Tuberculosis
  • Infant
  • Humans