The Population Pharmacokinetics of Meropenem in Adult Patients With Rifampicin-Sensitive Pulmonary Tuberculosis.
The Population Pharmacokinetics of Meropenem in Adult Patients With Rifampicin-Sensitive Pulmonary Tuberculosis.
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DOI：
10.3389/fphar.2021.637618
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发表时间：
2021
影响因子：
5.6
通讯作者：
Svensson EM
中科院分区：
文献类型：
--
作者：
Abulfathi AA;de Jager V;van Brakel E;Reuter H;Gupte N;Vanker N;Barnes GL;Nuermberger E;Dorman SE;Diacon AH;Dooley KE;Svensson EM
Background: Meropenem is being investigated for repurposing as an anti-tuberculosis drug. This study aimed to develop a meropenem population pharmacokinetics model in patients with pulmonary tuberculosis and identify covariates explaining inter-individual variability. Methods: Patients were randomized to one of four treatment groups: meropenem 2 g three times daily plus oral rifampicin 20 mg/kg once daily, meropenem 2 g three times daily, meropenem 1 g three times daily, and meropenem 3 g once daily. Meropenem was administered by intravenous infusion over 0.5–1 h. All patients also received oral amoxicillin/clavulanate together with each meropenem dose, and treatments continued daily for 14 days. Intensive plasma pharmacokinetics sampling over 8 h was conducted on the 14th day of the study. Nonlinear mixed-effects modeling was used for data analysis. The best model was chosen based on likelihood metrics, goodness-of-fit plots, and parsimony. Covariates were tested stepwise. Results: A total of 404 concentration measurements from 49 patients were included in the analysis. A two-compartment model parameterized with clearance (CL), inter-compartmental clearance (Q), and central (V1) and peripheral (V2) volumes of distribution fitted the data well. Typical values of CL, Q, V1, and V2 were 11.8 L/h, 3.26 L/h, 14.2 L, and 3.12 L, respectively. The relative standard errors of the parameter estimates ranged from 3.8 to 35.4%. The covariate relations included in the final model were creatinine clearance on CL and allometric scaling with body weight on all disposition parameters. An effect of age on CL as previously reported could not be identified. Conclusion: A two-compartment model described meropenem population pharmacokinetics in patients with pulmonary tuberculosis well. Covariates found to improve model fit were creatinine clearance and body weight but not rifampicin treatment. The final model will be used for an integrated pharmacokinetics/pharmacodynamics analysis linking meropenem exposure to early bactericidal activity.
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影响因子：
2.9
作者：
Li, Chonghua;Kuti, Joseph L.;Nicolau, David P.
通讯作者：
Nicolau, David P.
影响因子：
6.1
作者：
Lindbom, L;Pihlgren, P;Jonsson, N
通讯作者：
Jonsson, N
DOI：
10.1016/j.ijantimicag.2019.06.016
发表时间：
2019-09-01
影响因子：
10.8
作者：
Ehmann, Lisa;Zoller, Michael;Kloft, Charlotte
通讯作者：
Kloft, Charlotte
影响因子：
3.6
作者：
Dauby, Nicolas;Muylle, Inge;Payen, Marie-Christine
通讯作者：
Payen, Marie-Christine
DOI：
10.1002/psp4.12161
发表时间：
2017-02
期刊：
CPT: pharmacometrics & systems pharmacology
影响因子：
--
作者：
Nguyen TH;Mouksassi MS;Holford N;Al-Huniti N;Freedman I;Hooker AC;John J;Karlsson MO;Mould DR;Pérez Ruixo JJ;Plan EL;Savic R;van Hasselt JG;Weber B;Zhou C;Comets E;Mentré F;Model Evaluation Group of the International Society of Pharmacometrics (ISoP) Best Practice Committee
通讯作者：
Model Evaluation Group of the International Society of Pharmacometrics (ISoP) Best Practice Committee