Meropenem Plasma and Interstitial Soft Tissue Concentrations in Obese and Nonobese Patients—A Controlled Clinical Trial
Background: This controlled clinical study aimed to investigate the impact of obesity on plasma and tissue pharmacokinetics of meropenem. Methods: Obese (body mass index (BMI) ≥ 35 kg/m<sup>2</sup>) and age-/sex-matched nonobese (18.5 kg/m<sup>2</sup> ≥ BMI ≤ 30 kg/m<sup&g...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-12-01
|
| Series: | Antibiotics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2079-6382/9/12/931 |
| _version_ | 1797544001988984832 |
|---|---|
| author | Philipp Simon David Petroff David Busse Jana Heyne Felix Girrbach Arne Dietrich Alexander Kratzer Markus Zeitlinger Charlotte Kloft Frieder Kees Hermann Wrigge Christoph Dorn |
| author_facet | Philipp Simon David Petroff David Busse Jana Heyne Felix Girrbach Arne Dietrich Alexander Kratzer Markus Zeitlinger Charlotte Kloft Frieder Kees Hermann Wrigge Christoph Dorn |
| author_sort | Philipp Simon |
| collection | DOAJ |
| description | Background: This controlled clinical study aimed to investigate the impact of obesity on plasma and tissue pharmacokinetics of meropenem. Methods: Obese (body mass index (BMI) ≥ 35 kg/m<sup>2</sup>) and age-/sex-matched nonobese (18.5 kg/m<sup>2</sup> ≥ BMI ≤ 30 kg/m<sup>2</sup>) surgical patients received a short-term infusion of 1000-mg meropenem. Concentrations were determined via high performance liquid chromatography-ultraviolet (HPLC-UV) in the plasma and microdialysate from the interstitial fluid (ISF) of subcutaneous tissue up to eight h after dosing. An analysis was performed in the plasma and ISF by noncompartmental methods. Results: The maximum plasma concentrations in 15 obese (BMI 49 ± 11 kg/m<sup>2</sup>) and 15 nonobese (BMI 24 ± 2 kg/m<sup>2</sup>) patients were 54.0 vs. 63.9 mg/L (95% CI for difference: −18.3 to −3.5). The volume of distribution was 22.4 vs. 17.6 L, (2.6–9.1), but the clearance was comparable (12.5 vs. 11.1 L/h, −1.4 to 3.1), leading to a longer half-life (1.52 vs. 1.31 h, 0.05–0.37) and fairly similar area under the curve (AUC)<sub>8h</sub> (78.7 vs. 89.2 mg*h/L, −21.4 to 8.6). In the ISF, the maximum concentrations differed significantly (12.6 vs. 18.6 L, −16.8 to −0.8) but not the AUC<sub>8h</sub> (28.5 vs. 42.0 mg*h/L, −33.9 to 5.4). Time above the MIC (T > MIC) in the plasma and ISF did not differ significantly for MICs of 0.25–8 mg/L. Conclusions: In morbidly obese patients, meropenem has lower maximum concentrations and higher volumes of distribution. However, due to the slightly longer half-life, obesity has no influence on the T > MIC, so dose adjustments for obesity seem unnecessary. |
| first_indexed | 2024-03-10T13:53:27Z |
| format | Article |
| id | doaj.art-6442c100172c4f1590ef2a4b1170fd99 |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-10T13:53:27Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-6442c100172c4f1590ef2a4b1170fd992023-11-21T01:53:08ZengMDPI AGAntibiotics2079-63822020-12-0191293110.3390/antibiotics9120931Meropenem Plasma and Interstitial Soft Tissue Concentrations in Obese and Nonobese Patients—A Controlled Clinical TrialPhilipp Simon0David Petroff1David Busse2Jana Heyne3Felix Girrbach4Arne Dietrich5Alexander Kratzer6Markus Zeitlinger7Charlotte Kloft8Frieder Kees9Hermann Wrigge10Christoph Dorn11Department of Anaesthesiology and Intensive Care Medicine, University of Leipzig Medical Centre, 04103 Leipzig, GermanyIntegrated Research and Treatment Center (IFB) Adiposity Diseases, University of Leipzig, 04103 Leipzig, GermanyDepartment of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universitaet Berlin, 12169 Berlin, GermanyDepartment of Anaesthesiology and Intensive Care Medicine, University of Leipzig Medical Centre, 04103 Leipzig, GermanyDepartment of Anaesthesiology and Intensive Care Medicine, University of Leipzig Medical Centre, 04103 Leipzig, GermanyIntegrated Research and Treatment Center (IFB) Adiposity Diseases, University of Leipzig, 04103 Leipzig, GermanyInstitute of Pharmacy, University of Regensburg, 93053 Regensburg, GermanyDepartment of Clinical Pharmacology, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universitaet Berlin, 12169 Berlin, GermanyDepartment of Pharmacology, University of Regensburg, 93053 Regensburg, GermanyDepartment of Anaesthesiology and Intensive Care Medicine, University of Leipzig Medical Centre, 04103 Leipzig, GermanyInstitute of Pharmacy, University of Regensburg, 93053 Regensburg, GermanyBackground: This controlled clinical study aimed to investigate the impact of obesity on plasma and tissue pharmacokinetics of meropenem. Methods: Obese (body mass index (BMI) ≥ 35 kg/m<sup>2</sup>) and age-/sex-matched nonobese (18.5 kg/m<sup>2</sup> ≥ BMI ≤ 30 kg/m<sup>2</sup>) surgical patients received a short-term infusion of 1000-mg meropenem. Concentrations were determined via high performance liquid chromatography-ultraviolet (HPLC-UV) in the plasma and microdialysate from the interstitial fluid (ISF) of subcutaneous tissue up to eight h after dosing. An analysis was performed in the plasma and ISF by noncompartmental methods. Results: The maximum plasma concentrations in 15 obese (BMI 49 ± 11 kg/m<sup>2</sup>) and 15 nonobese (BMI 24 ± 2 kg/m<sup>2</sup>) patients were 54.0 vs. 63.9 mg/L (95% CI for difference: −18.3 to −3.5). The volume of distribution was 22.4 vs. 17.6 L, (2.6–9.1), but the clearance was comparable (12.5 vs. 11.1 L/h, −1.4 to 3.1), leading to a longer half-life (1.52 vs. 1.31 h, 0.05–0.37) and fairly similar area under the curve (AUC)<sub>8h</sub> (78.7 vs. 89.2 mg*h/L, −21.4 to 8.6). In the ISF, the maximum concentrations differed significantly (12.6 vs. 18.6 L, −16.8 to −0.8) but not the AUC<sub>8h</sub> (28.5 vs. 42.0 mg*h/L, −33.9 to 5.4). Time above the MIC (T > MIC) in the plasma and ISF did not differ significantly for MICs of 0.25–8 mg/L. Conclusions: In morbidly obese patients, meropenem has lower maximum concentrations and higher volumes of distribution. However, due to the slightly longer half-life, obesity has no influence on the T > MIC, so dose adjustments for obesity seem unnecessary.https://www.mdpi.com/2079-6382/9/12/931antibiotic dosingconcentrationsmeropenemmicrodialysisobesitypharmacokinetics |
| spellingShingle | Philipp Simon David Petroff David Busse Jana Heyne Felix Girrbach Arne Dietrich Alexander Kratzer Markus Zeitlinger Charlotte Kloft Frieder Kees Hermann Wrigge Christoph Dorn Meropenem Plasma and Interstitial Soft Tissue Concentrations in Obese and Nonobese Patients—A Controlled Clinical Trial Antibiotics antibiotic dosing concentrations meropenem microdialysis obesity pharmacokinetics |
| title | Meropenem Plasma and Interstitial Soft Tissue Concentrations in Obese and Nonobese Patients—A Controlled Clinical Trial |
| title_full | Meropenem Plasma and Interstitial Soft Tissue Concentrations in Obese and Nonobese Patients—A Controlled Clinical Trial |
| title_fullStr | Meropenem Plasma and Interstitial Soft Tissue Concentrations in Obese and Nonobese Patients—A Controlled Clinical Trial |
| title_full_unstemmed | Meropenem Plasma and Interstitial Soft Tissue Concentrations in Obese and Nonobese Patients—A Controlled Clinical Trial |
| title_short | Meropenem Plasma and Interstitial Soft Tissue Concentrations in Obese and Nonobese Patients—A Controlled Clinical Trial |
| title_sort | meropenem plasma and interstitial soft tissue concentrations in obese and nonobese patients a controlled clinical trial |
| topic | antibiotic dosing concentrations meropenem microdialysis obesity pharmacokinetics |
| url | https://www.mdpi.com/2079-6382/9/12/931 |
| work_keys_str_mv | AT philippsimon meropenemplasmaandinterstitialsofttissueconcentrationsinobeseandnonobesepatientsacontrolledclinicaltrial AT davidpetroff meropenemplasmaandinterstitialsofttissueconcentrationsinobeseandnonobesepatientsacontrolledclinicaltrial AT davidbusse meropenemplasmaandinterstitialsofttissueconcentrationsinobeseandnonobesepatientsacontrolledclinicaltrial AT janaheyne meropenemplasmaandinterstitialsofttissueconcentrationsinobeseandnonobesepatientsacontrolledclinicaltrial AT felixgirrbach meropenemplasmaandinterstitialsofttissueconcentrationsinobeseandnonobesepatientsacontrolledclinicaltrial AT arnedietrich meropenemplasmaandinterstitialsofttissueconcentrationsinobeseandnonobesepatientsacontrolledclinicaltrial AT alexanderkratzer meropenemplasmaandinterstitialsofttissueconcentrationsinobeseandnonobesepatientsacontrolledclinicaltrial AT markuszeitlinger meropenemplasmaandinterstitialsofttissueconcentrationsinobeseandnonobesepatientsacontrolledclinicaltrial AT charlottekloft meropenemplasmaandinterstitialsofttissueconcentrationsinobeseandnonobesepatientsacontrolledclinicaltrial AT friederkees meropenemplasmaandinterstitialsofttissueconcentrationsinobeseandnonobesepatientsacontrolledclinicaltrial AT hermannwrigge meropenemplasmaandinterstitialsofttissueconcentrationsinobeseandnonobesepatientsacontrolledclinicaltrial AT christophdorn meropenemplasmaandinterstitialsofttissueconcentrationsinobeseandnonobesepatientsacontrolledclinicaltrial |