In:
Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 59, No. 10 ( 2015-10), p. 6073-6079
Abstract:
Ofloxacin is widely used for the treatment of multidrug-resistant tuberculosis (MDR-TB). Data on its pharmacokinetics and safety in children are limited. It is not known whether the current internationally recommended pediatric dosage of 15 to 20 mg/kg of body weight achieves exposures reached in adults with tuberculosis after a standard 800-mg dose (adult median area under the concentration-time curve from 0 to 24 h [AUC 0–24 ], 103 μg · h/ml). We assessed the pharmacokinetics and safety of ofloxacin in children 〈 15 years old routinely receiving ofloxacin for MDR-TB treatment or preventive therapy. Plasma samples were collected predose and at 1, 2, 4, 8, and either 6 or 11 h after a 20-mg/kg dose. Pharmacokinetic parameters were calculated using noncompartmental analysis. Children with MDR-TB disease underwent long-term safety monitoring. Of 85 children (median age, 3.4 years), 11 (13%) were HIV infected, and of 79 children with evaluable data, 14 (18%) were underweight. The ofloxacin mean (range) maximum concentration ( C max ), AUC 0–8 , and half-life were 8.97 μg/ml (2.47 to 14.4), 44.2 μg · h/ml (12.1 to 75.8), and 3.49 h (1.89 to 6.95), respectively. The mean AUC 0–24 , estimated in 72 participants, was 66.7 μg · h/ml (range, 18.8 to 120.7). In multivariable analysis, AUC 0–24 was increased by 1.46 μg · h/ml for each 1-kg increase in body weight (95% confidence interval [CI], 0.44 to 2.47; P = 0.006); no other assessed variable contributed to the model. No grade 3 or 4 events at least possibly attributed to ofloxacin were observed. Ofloxacin was safe and well tolerated in children with MDR-TB, but exposures were well below reported adult values, suggesting that dosage modification may be required to optimize MDR-TB treatment regimens in children.
Type of Medium:
Online Resource
ISSN:
0066-4804
,
1098-6596
DOI:
10.1128/AAC.01404-15
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
2015
detail.hit.zdb_id:
1496156-8
detail.hit.zdb_id:
217602-6
SSG:
12
SSG:
15,3
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