期刊
CLINICAL INFECTIOUS DISEASES
卷 67, 期 -, 页码 S327-S335出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/cid/ciy625
关键词
pharmacokinetics/pharmacodynamics; optimal dose; Monte Carlo simulation; probability of target attainment
资金
- Baylor Institute of Immunology Research of the Baylor Research Institute
Linezolid has been successfully used for treatment of multidrug-resistant tuberculosis (MDR-TB). However, dose-and durationrelated toxicity limit its use. Here, our aim was to search relevant pharmacokinetics (PK)/pharmacodynamics (PD) literature to identify the effective PK/PD index and to define the optimal daily dose and dosing frequency of linezolid in MDR-TB regimens. The systematic search resulted in 8 studies that met inclusion criteria. A significant PK variability was observed. Efficacy of linezolid seems to be driven by area under the concentration-time curve (AUC)/minimum inhibitory concentration (MIC). Literature is inconclusive about the preferred administration of a daily dose of 600 mg. To prevent development of drug resistance, an AUC/MIC ratio of 100 in the presence of a companion drug at relevant exposure is required. A daily dose of 600 mg seems appropriate to balance between efficacy and toxicity. Being a drug with a very narrow therapeutic window, linezolid treatment may benefit from a more personalized approach, that is, measuring actual MIC values and therapeutic drug monitoring.
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