Details:

Alternative Title:
Pediatr Infect Dis J
Personal Author:
Mase, Sundari R. ; Jereb, John A. ; Gonzalez, Daniel ; Martin, Fatma ; Daley, Charles L. ; ... More +
Mase, Sundari R. ; Jereb, John A. ; Gonzalez, Daniel ; Martin, Fatma ; Daley, Charles L. ; Fred, Dorina ; Loeffler, Ann ; Menon, Lakshmy ; Morris, Sapna Bamrah ; Brostrom, Richard ; Chorba, Terence ; Peloquin, Charles A. Less -
Description:
Background

In the Federated States of Micronesia (FSM) and then the Republic of the Marshall Islands (RMI), levofloxacin pharmacokinetics (PK) 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 (MDR TB) disease or latent infection after MDR TB 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 levofloxacin Cmax, elimination half-life (t1/2), and area under the curve from 0 to 24 hours (AUC0–24 hours * µg/mL) were correlated to determine optimal dosage and to examine associations. Population PK and target attainment were modeled. With results from FSM, dosages were increased in RMI toward the target maximal drug concentration (Cmax) for Mycobacterium tuberculosis, 8–12 µg/ml.

Results

Cmax correlated linearly with per-weight dosage. Neither Cmax nor t1/2 was associated with gender, age, body mass index, concurrent medications, or pre-dose 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.


Subjects:
[+]
Adolescent Anti-Bacterial Agents Article Child Child, Preschool Drug Monitoring Female Humans Infant Latent Tuberculosis Levofloxacin Male Microbial Sensitivity Tests Mycobacterium Tuberculosis Tuberculosis, Multidrug-Resistant
Source:
Pediatr Infect Dis J. 35(4):414-421.
Pubmed ID:
26658531
Pubmed Central ID:
PMC5117358
Document Type:
Journal Article
Funding:
CC999999/Intramural CDC HHS/United States ; T32 GM086330/GM/NIGMS NIH HHS/United States ; UL1 TR001427/TR/NCATS NIH HHS/United States ; T32GM086330/GM/NIGMS NIH HHS/United States
CC999999/Intramural CDC HHS/United States ; T32 GM086330/GM/NIGMS NIH HHS/United States ; UL1 TR001427/TR/NCATS NIH HHS/United States ; T32GM086330/GM/NIGMS NIH HHS/United States Less -
Place as Subject:
Micronesia
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:922b4b4ebe335c6290609698dfd48c71d8733bbb7d1974de48f2ba8c78709f8c
Download URL:
https://stacks.cdc.gov/view/cdc/43102/cdc_43102_DS1.pdf
File Type:

Supporting Files

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