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Measurement of soft tissue drug concentrations in morbidly obese and non-obese patients – A prospective, parallel group, open-labeled, controlled, phase IV, single center clinical trial()

BACKGROUND: Pharmacokinetic (PK) and pharmacodynamic (PD) data on perioperative antibiotic prophylaxis or antibiotic therapy are rare in patients suffering from morbid obesity. Furthermore, dosing regimens should be based on PK/PD models that ensure effective antibiotic exposure not in plasma, but p...

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Autores principales: Simon, P., Petroff, D., Dorn, C., Ehmann, L., Kloft, C., Prettin, C., Dietrich, A., Zeitlinger, M., Kees, F., Wrigge, H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6535681/
https://www.ncbi.nlm.nih.gov/pubmed/31193565
http://dx.doi.org/10.1016/j.conctc.2019.100375
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author Simon, P.
Petroff, D.
Dorn, C.
Ehmann, L.
Kloft, C.
Prettin, C.
Dietrich, A.
Zeitlinger, M.
Kees, F.
Wrigge, H.
author_facet Simon, P.
Petroff, D.
Dorn, C.
Ehmann, L.
Kloft, C.
Prettin, C.
Dietrich, A.
Zeitlinger, M.
Kees, F.
Wrigge, H.
author_sort Simon, P.
collection PubMed
description BACKGROUND: Pharmacokinetic (PK) and pharmacodynamic (PD) data on perioperative antibiotic prophylaxis or antibiotic therapy are rare in patients suffering from morbid obesity. Furthermore, dosing regimens should be based on PK/PD models that ensure effective antibiotic exposure not in plasma, but primarily at the site of infection, mostly in the interstitial fluid (ISF). The aim of this trial is to investigate whether current dosing regimens of various antibiotics lead to effective concentrations in the ISF of morbidly obese patients. METHODS: We designed a prospective, parallel group, open-labeled, controlled single center trial to investigate the plasma and tissue pharmacokinetics of the antibiotics linezolid, meropenem, tigecycline, piperacillin/tazobactam, fosfomcyine, cefazolin, metronidazole and as secondary aim the analgesics metamizole and acetaminophen. Inclusion criteria comprise body mass index ≥35 kg/m(2) for obese or between 18.5 and 30 kg/m(2) for non-obese patients scheduled for elective abdominal surgery. For PK analysis, blood and microdialysate samples of subcutaneous tissue were collected 0–8 h after study drug administration. The primary endpoint is to investigate a possible dependency of the area-under-the-curve (AUC(0-8)) in the interstitial fluid on body weight and obesity with population based pharmacokinetic analysis. DISCUSSION: Inadequate dosing regimes of antibiotics may be a relevant factor for morbidity and mortality of patients, as well as for the development of bacterial antibiotic resistance. The measurement of plasma and tissue concentrations will provide information necessary for PK/PD-modelling. These data about antibiotic PK/PDcharacteristics in soft tissue and their dependence on weight should help to develop weight-dependent models for calculation of patient's individual doses of different antibiotics. TRIAL REGISTRATION: EU clinical trials register (EudraCT-No. 2012-004383-22) and German Clinical trials Register (DRKS00004776);
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spelling pubmed-65356812019-05-30 Measurement of soft tissue drug concentrations in morbidly obese and non-obese patients – A prospective, parallel group, open-labeled, controlled, phase IV, single center clinical trial() Simon, P. Petroff, D. Dorn, C. Ehmann, L. Kloft, C. Prettin, C. Dietrich, A. Zeitlinger, M. Kees, F. Wrigge, H. Contemp Clin Trials Commun Article BACKGROUND: Pharmacokinetic (PK) and pharmacodynamic (PD) data on perioperative antibiotic prophylaxis or antibiotic therapy are rare in patients suffering from morbid obesity. Furthermore, dosing regimens should be based on PK/PD models that ensure effective antibiotic exposure not in plasma, but primarily at the site of infection, mostly in the interstitial fluid (ISF). The aim of this trial is to investigate whether current dosing regimens of various antibiotics lead to effective concentrations in the ISF of morbidly obese patients. METHODS: We designed a prospective, parallel group, open-labeled, controlled single center trial to investigate the plasma and tissue pharmacokinetics of the antibiotics linezolid, meropenem, tigecycline, piperacillin/tazobactam, fosfomcyine, cefazolin, metronidazole and as secondary aim the analgesics metamizole and acetaminophen. Inclusion criteria comprise body mass index ≥35 kg/m(2) for obese or between 18.5 and 30 kg/m(2) for non-obese patients scheduled for elective abdominal surgery. For PK analysis, blood and microdialysate samples of subcutaneous tissue were collected 0–8 h after study drug administration. The primary endpoint is to investigate a possible dependency of the area-under-the-curve (AUC(0-8)) in the interstitial fluid on body weight and obesity with population based pharmacokinetic analysis. DISCUSSION: Inadequate dosing regimes of antibiotics may be a relevant factor for morbidity and mortality of patients, as well as for the development of bacterial antibiotic resistance. The measurement of plasma and tissue concentrations will provide information necessary for PK/PD-modelling. These data about antibiotic PK/PDcharacteristics in soft tissue and their dependence on weight should help to develop weight-dependent models for calculation of patient's individual doses of different antibiotics. TRIAL REGISTRATION: EU clinical trials register (EudraCT-No. 2012-004383-22) and German Clinical trials Register (DRKS00004776); Elsevier 2019-05-10 /pmc/articles/PMC6535681/ /pubmed/31193565 http://dx.doi.org/10.1016/j.conctc.2019.100375 Text en © 2019 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Simon, P.
Petroff, D.
Dorn, C.
Ehmann, L.
Kloft, C.
Prettin, C.
Dietrich, A.
Zeitlinger, M.
Kees, F.
Wrigge, H.
Measurement of soft tissue drug concentrations in morbidly obese and non-obese patients – A prospective, parallel group, open-labeled, controlled, phase IV, single center clinical trial()
title Measurement of soft tissue drug concentrations in morbidly obese and non-obese patients – A prospective, parallel group, open-labeled, controlled, phase IV, single center clinical trial()
title_full Measurement of soft tissue drug concentrations in morbidly obese and non-obese patients – A prospective, parallel group, open-labeled, controlled, phase IV, single center clinical trial()
title_fullStr Measurement of soft tissue drug concentrations in morbidly obese and non-obese patients – A prospective, parallel group, open-labeled, controlled, phase IV, single center clinical trial()
title_full_unstemmed Measurement of soft tissue drug concentrations in morbidly obese and non-obese patients – A prospective, parallel group, open-labeled, controlled, phase IV, single center clinical trial()
title_short Measurement of soft tissue drug concentrations in morbidly obese and non-obese patients – A prospective, parallel group, open-labeled, controlled, phase IV, single center clinical trial()
title_sort measurement of soft tissue drug concentrations in morbidly obese and non-obese patients – a prospective, parallel group, open-labeled, controlled, phase iv, single center clinical trial()
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6535681/
https://www.ncbi.nlm.nih.gov/pubmed/31193565
http://dx.doi.org/10.1016/j.conctc.2019.100375
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