Pharmacokinetics of rifampicin in adult TB patients and healthy volunteers: a systematic review and meta-analysis.
Pharmacokinetics of rifampicin in adult TB patients and healthy volunteers: a systematic review and meta-analysis.
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DOI：
10.1093/jac/dky152
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发表时间：
2018-09-01
期刊：
影响因子：
--
通讯作者：
Davies G
中科院分区：
文献类型：
--
作者：
Stott KE;Pertinez H;Sturkenboom MGG;Boeree MJ;Aarnoutse R;Ramachandran G;Requena-Méndez A;Peloquin C;Koegelenberg CFN;Alffenaar JWC;Ruslami R;Tostmann A;Swaminathan S;McIlleron H;Davies G
本研究的目的是探索口服利福平药代动力学（PK）的研究间异质性，推导标准剂量下利福平PK参数的汇总估计值，并将其与较高剂量的汇总估计值进行比较。 对截至2017年5月以英文发表的利福平PK研究进行了系统检索。提取描述Cmax和AUC的数据。荟萃分析提供了标准利福平剂量下PK参数估计值的汇总估计值。通过I2统计量的估计和森林样地的目视检查来评估异质性。使用临床前药效学（PD）数据，以图形方式比较标准剂量和更高剂量下的AUC估计值。PK参数的显著异质性是明显的，并在荟萃回归中得到支持。治疗持续时间对利福平PK参数的汇总估计值有显著影响，单次给药后Cmax为8.98 mg/L（SEM 2.19），稳态给药后Cmax为5.79 mg/L（SEM 2.14），单次和稳态给药后AUC分别为72.56 mg·h/L（SEM 2.60）和38.73 mg·h/L（SEM 4.33）。达到临床前研究中定义的血浆PK/PD目标需要至少25 mg/kg的利福平剂量。利福平PK参数估计值存在巨大的研究间异质性。可用的修改变量无法解释这一点。应增加利福平的推荐剂量以提高疗效。本研究为理解标准剂量下利福平的PK提供了重要的参考点，因为在该领域继续努力探索更高的剂量策略。
The objectives of this study were to explore inter-study heterogeneity in the pharmacokinetics (PK) of orally administered rifampicin, to derive summary estimates of rifampicin PK parameters at standard dosages and to compare these with summary estimates for higher dosages. A systematic search was performed for studies of rifampicin PK published in the English language up to May 2017. Data describing the Cmax and AUC were extracted. Meta-analysis provided summary estimates for PK parameter estimates at standard rifampicin dosages. Heterogeneity was assessed by estimation of the I2 statistic and visual inspection of forest plots. Summary AUC estimates at standard and higher dosages were compared graphically and contextualized using preclinical pharmacodynamic (PD) data. Substantial heterogeneity in PK parameters was evident and upheld in meta-regression. Treatment duration had a significant impact on the summary estimates for rifampicin PK parameters, with Cmax 8.98 mg/L (SEM 2.19) after a single dose and 5.79 mg/L (SEM 2.14) at steady-state dosing, and AUC 72.56 mg·h/L (SEM 2.60) and 38.73 mg·h/L (SEM 4.33) after single and steady-state dosing, respectively. Rifampicin dosages of at least 25 mg/kg are required to achieve plasma PK/PD targets defined in preclinical studies. Vast inter-study heterogeneity exists in rifampicin PK parameter estimates. This is not explained by the available modifying variables. The recommended dosage of rifampicin should be increased to improve efficacy. This study provides an important point of reference for understanding rifampicin PK at standard dosages as efforts to explore higher dosing strategies continue in this field.
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期刊：
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影响因子：
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作者：
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通讯作者：
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DOI：
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发表时间：
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影响因子：
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