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The Population Phar...
The Population Pharmacokinetics of Meropenem in Adult Patients With Rifampicin-Sensitive Pulmonary Tuberculosis
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- Abulfathi, Ahmed A. (författare)
- Stellenbosch Univ, Fac Med & Hlth Sci, Dept Med, Div Clin Pharmacol, Stellenbosch, South Africa.;Univ Maiduguri, Coll Med Sci, Dept Clin Pharmacol & Therapeut, Maiduguri, Nigeria.
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- de Jager, Veronique (författare)
- Task Appl Sci, Bellville, South Africa.
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- van Brakel, Elana (författare)
- Task Appl Sci, Bellville, South Africa.
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- Reuter, Helmuth (författare)
- Stellenbosch Univ, Fac Med & Hlth Sci, Dept Med, Div Clin Pharmacol, Stellenbosch, South Africa.
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- Gupte, Nikhil (författare)
- Johns Hopkins Univ, Dept Med, Ctr TB Res, Baltimore, MD USA.
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- Vanker, Naadira (författare)
- Task Appl Sci, Bellville, South Africa.
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- Barnes, Grace L. (författare)
- Johns Hopkins Univ, Dept Med, Ctr TB Res, Baltimore, MD USA.
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- Nuermberger, Eric (författare)
- Johns Hopkins Univ, Dept Med, Ctr TB Res, Baltimore, MD USA.
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- Dorman, Susan E. (författare)
- Med Univ South Carolina, Dept Med, Charleston, SC USA.
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- Diacon, Andreas H. (författare)
- Task Appl Sci, Bellville, South Africa.;Stellenbosch Univ, Fac Med & Hlth Sci, Dept Med, Stellenbosch, South Africa.
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- Dooley, Kelly E. (författare)
- Johns Hopkins Univ, Div Clin Pharmacol, Dept Med, Ctr TB Res, Baltimore, MD USA.;Johns Hopkins Univ, Div Infect Dis, Dept Med, Ctr TB Res, Baltimore, MD USA.
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- Svensson, Elin, 1985- (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Radboud Univ Nijmegen, Radboud Inst Hlth Sci, Dept Pharm, Med Ctr, Nijmegen, Netherlands.
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Stellenbosch Univ, Fac Med & Hlth Sci, Dept Med, Div Clin Pharmacol, Stellenbosch, South Africa;Univ Maiduguri, Coll Med Sci, Dept Clin Pharmacol & Therapeut, Maiduguri, Nigeria. Task Appl Sci, Bellville, South Africa. (creator_code:org_t)
- 2021-06-29
- 2021
- Engelska.
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Ingår i: Frontiers in Pharmacology. - : Frontiers Media S.A.. - 1663-9812. ; 12
- Relaterad länk:
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https://doi.org/10.3...
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https://uu.diva-port... (primary) (Raw object)
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https://www.frontier...
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https://urn.kb.se/re...
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https://doi.org/10.3...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Nyckelord
- meropenem
- population pharmacokinetic (PK) model
- tuberculosis
- pharmacokinetics analysis
- drug sensitive TB
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- Av författaren/redakt...
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Abulfathi, Ahmed ...
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de Jager, Veroni ...
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van Brakel, Elan ...
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Reuter, Helmuth
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Gupte, Nikhil
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Vanker, Naadira
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Barnes, Grace L.
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Nuermberger, Eri ...
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Dorman, Susan E.
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Diacon, Andreas ...
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Dooley, Kelly E.
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Svensson, Elin, ...
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