期刊
CLINICAL PHARMACOLOGY & THERAPEUTICS
卷 98, 期 6, 页码 622-629出版社
WILEY
DOI: 10.1002/cpt.202
关键词
-
资金
- Eunice Kennedy Shriver National Institute of Child Health and Human Development [R01HD074944]
- Bristol-Myers Squibb Secure the Future Foundation
- South African National Research Foundation
- NIH/NIAID [UM1AI069465]
- KNAW
- ANDALAN UNPAD research grant
- National Institutes of Health [R01: 069169-01]
- German Leprosy and Tuberculosis Relief Association
- VIDI grant from the Netherlands Foundation for Scientific Research
- MRC [MR/M007340/1] Funding Source: UKRI
- Medical Research Council [MR/M007340/1] Funding Source: researchfish
Pediatric tuberculous meningitis (TBM) is a highly morbid, often fatal disease. Standard treatment includes isoniazid, rifampin, pyrazinamide, and ethambutol. Current rifampin dosing achieves low cerebrospinal fluid (CSF) concentrations, and CSF penetration of ethambutol is poor. In adult trials, higher-dose rifampin and/or a fluoroquinolone reduced mortality and disability. To estimate optimal dosing of rifampin and levofloxacin for children, we compiled plasma and CSF pharmacokinetic (PK) and outcomes data from adult TBM trials plus plasma PK data from children. A population PK/pharmacodynamic (PD) model using adult data defined rifampin target exposures (plasma area under the curve (AUC)(0-24) = 92 mg(star)h/L). Levofloxacin targets and rifampin pediatric drug disposition information were literature-derived. To attain target rifampin exposures, children require daily doses of at least 30 mg/kg orally or 15 mg/kg intravenously (i.v.). From our pediatric population PK model, oral levofloxacin doses needed to attain exposure targets were 19-33 mg/kg. Our results provide data-driven guidance to maximize pediatric TBM treatment while we await definitive trial results.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据