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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
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4 2016
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Source: Pediatr Infect Dis J. 35(4):414-421
[PDF-1.64 MB]
Details:
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Alternative Title:Pediatr Infect Dis J
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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.
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Pubmed ID:26658531
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Pubmed Central ID:PMC5117358
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