Dosing Regimens of Cotrimoxazole (Trimethoprim-Sulfamethoxazole) for Melioidosis
Dosing Regimens of Cotrimoxazole (Trimethoprim-Sulfamethoxazole) for Melioidosis
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DOI：
10.1128/aac.01301-08
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发表时间：
2009-10-01
影响因子：
4.9
通讯作者：
Peacock, Sharon J.
中科院分区：
文献类型：
--
作者：
Cheng, Allen C.;McBryde, Emma S.;Peacock, Sharon J.
类鼻疽是一种感染性疾病，尽管延长抗生素根除治疗12至20周，仍有复发倾向。进行了药代动力学（PK）模拟研究，以确定泰国和澳大利亚当前根除方案中使用的复方新诺明（甲氧苄啶-磺胺甲恶唑[TMP-SMX]）的最佳剂量。生物利用度、蛋白结合率以及吸收和消除系数的数据来自已发表的文献。表观分布容积与体重相关，并分别估计泰国和澳大利亚人群。体外实验证明了浓度依赖性杀伤。在澳大利亚，目前使用的根除方案预计（320 [TMP]/1，600 [SMX] mg，每12 h [q12 h]一次）可达到PK药效学（PD）目标（TMP和SMX 0 - 24 h浓度-时间曲线下面积/MIC比值>25）（= 1/19 mg/L），但最近实施的基于体重的方案（60 kg，320/1，600 mg q12 h）预计将达到MIC为
Melioidosis is an infectious disease with a propensity for relapse, despite prolonged antibiotic eradication therapy for 12 to 20 weeks. A pharmacokinetic (PK) simulation study was performed to determine the optimal dosing of cotrimoxazole (trimethoprim-sulfamethoxazole [TMP-SMX]) used in current eradication regimens in Thailand and Australia. Data for bioavailability, protein binding, and coefficients of absorption and elimination were taken from published literature. Apparent volumes of distribution were correlated with body mass and were estimated separately for Thai and Australian populations. In vitro experiments demonstrated concentration-dependent killing. In Australia, the currently used eradication regimen ( 320 [TMP]/1,600 [SMX] mg every 12 h [q12h]) was predicted to achieve the PK-pharmacodynamic (PD) target ( an area under the concentration-time curve from 0 to 24 h/MIC ratio of >25 for both TMP and SMX) for strains with the MIC90 of Australian strains (= 1/19 mg/liter, but the recently implemented weight-based regimen (60 kg, 320/1,600 mg q12h) would be expected to achieve adequate concentrations for strains with an MIC of