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Optimizing study de...
Optimizing study design in LPS challenge studies for quantifying drug induced inhibition of TNF? response: Did we miss the prime time?
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- Larsson, Julia (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för matematiska vetenskaper,Department of Mathematical Sciences,University of Gothenburg,Stiftelsen Fraunhofer-Chalmers Centrum för Industrimatematik (FCC),Fraunhofer-Chalmers Research Centre for Industrial Mathematics (FCC),Chalmers tekniska högskola,Chalmers University of Technology
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- Hoppe, E. (författare)
- Grünenthal GmbH
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- Gautrois, M. (författare)
- Grünenthal GmbH
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- Cvijovic, Marija, 1977 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för matematiska vetenskaper, Tillämpad matematik och statistik,Department of Mathematical Sciences, Applied Mathematics and Statistics,Chalmers tekniska högskola,Chalmers University of Technology,University of Gothenburg
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- Jirstrand, Mats, 1968 (författare)
- Stiftelsen Fraunhofer-Chalmers Centrum för Industrimatematik (FCC),Fraunhofer-Chalmers Research Centre for Industrial Mathematics (FCC)
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(creator_code:org_t)
- Elsevier BV, 2022
- 2022
- Engelska.
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Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 176
- Relaterad länk:
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https://research.cha... (primary) (free)
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- In this work we evaluate the study design of LPS challenge experiments used for quantification of drug induced inhibition of TNF alpha response and provide general guidelines of how to improve the study design. Analysis of model simulated data, using a recently published TNF alpha turnover model, as well as the optimal design tool PopED have been used to find the optimal values of three key study design variables - time delay between drug and LPS administration, LPS dose, and sampling time points - that in turn could make the resulting TNF alpha response data more informative. Our findings suggest that the current rule of thumb for choosing the time delay should be reconsidered, and that the placement of the measurements after maximal TNF alpha response are crucial for the quality of the experiment. Furthermore, a literature study summarizing a wide range of published LPS challenge studies is provided, giving a broader perspective of how LPS challenge studies are usually conducted both in a preclinical and clinical setting.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
- TEKNIK OCH TEKNOLOGIER -- Medicinteknik -- Medicinsk laboratorie- och mätteknik (hsv//swe)
- ENGINEERING AND TECHNOLOGY -- Medical Engineering -- Medical Laboratory and Measurements Technologies (hsv//eng)
- TEKNIK OCH TEKNOLOGIER -- Annan teknik -- Övrig annan teknik (hsv//swe)
- ENGINEERING AND TECHNOLOGY -- Other Engineering and Technologies -- Other Engineering and Technologies not elsewhere specified (hsv//eng)
Nyckelord
- Tumor necrosis factor alpha
- Lipopolysaccharides
- Pharmacokinetics and
- pharmacodynamics
- Non-linear mixed effects modeling
- Optimal design
- alpha
- model
- Lipopolysaccharides
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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