A model-based analysis identifies differences in phenotypic resistance between in vitro and in vivo: implications for translational medicine within tuberculosis.

↓ Direkt till sidans innehåll
↓ Direkt till sidans sekundära innehåll (sidomenyn)

Search: WFRF:(Coates Alan S) > (2020) > A model-based analy...

1 of 1
Previous record
Next record
To hitlist

Details
MARC

Clewe, OskarUppsala universitet,Institutionen för farmaceutisk biovetenskap (author)

A model-based analysis identifies differences in phenotypic resistance between in vitro and in vivo : implications for translational medicine within tuberculosis.

Article/chapterEnglish2020

Publisher, publication year, extent ...

2020-06-01
Springer Science and Business Media LLC,2020
electronicrdacarrier

Numbers

LIBRIS-ID:oai:DiVA.org:uu-429938
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-429938URI
https://doi.org/10.1007/s10928-020-09694-0DOI

Supplementary language notes

Language:English
Summary in:English

Part of subdatabase

SwePubSwePub

Classification

Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

Notes

Proper characterization of drug effects on Mycobacterium tuberculosis relies on the characterization of phenotypically resistant bacteria to correctly establish exposure-response relationships. The aim of this work was to evaluate the potential difference in phenotypic resistance in in vitro compared to murine in vivo models using CFU data alone or CFU together with most probable number (MPN) data following resuscitation with culture supernatant. Predictions of in vitro and in vivo phenotypic resistance i.e. persisters, using the Multistate Tuberculosis Pharmacometric (MTP) model framework was evaluated based on bacterial cultures grown with and without drug exposure using CFU alone or CFU plus MPN data. Phenotypic resistance and total bacterial number in in vitro natural growth observations, i.e. without drug, was well predicted by the MTP model using only CFU data. Capturing the murine in vivo total bacterial number and persisters during natural growth did however require re-estimation of model parameter using both the CFU and MPN observations implying that the ratio of persisters to total bacterial burden is different in vitro compared to murine in vivo. The evaluation of the in vitro rifampicin drug effect revealed that higher resolution in the persister drug effect was seen using CFU and MPN compared to CFU alone although drug effects on the other bacterial populations were well predicted using only CFU data. The ratio of persistent bacteria to total bacteria was predicted to be different between in vitro and murine in vivo. This difference could have implications for subsequent translational efforts in tuberculosis drug development.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Infektionsmedicin hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Infectious Medicine hsv//eng
Pharmacodynamics
Phenotypic resistance
Translational modelling
Tuberculosis

Added entries (persons, corporate bodies, meetings, titles ...)

Faraj, AlanUppsala universitet,Institutionen för farmaceutisk biovetenskap(Swepub:uu)alafa430 (author)
Hu, Yanmin (author)
Coates, Anthony R M (author)
Simonsson, Ulrika S. H.,ProfessorUppsala universitet,Institutionen för farmaceutisk biovetenskap(Swepub:uu)usv12211 (author)
Uppsala universitetInstitutionen för farmaceutisk biovetenskap (creator_code:org_t)

Related titles

In:Journal of Pharmacokinetics and Pharmacodynamics: Springer Science and Business Media LLC47:5, s. 421-4301567-567X1573-8744

Internet link

Find in a library

Journal of Pharmacokinetics and Pharmacodynamics (Search for host publication in LIBRIS)

To the university's database

1 of 1
Previous record
Next record
To hitlist

Find more in SwePub

By the author/editor: Clewe, Oskar; Faraj, Alan; Hu, Yanmin; Coates, Anthony ...; Simonsson, Ulrik ...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Infectious Medic ...

Articles in the publication: Journal of Pharm ...

By the university: Uppsala University

Search outside SwePub

Extend your search to:: Google; Google Book Search; Google Scholar

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

LIBRIS.kb.se