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Can a pharmacokinet...
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Nielsen, Elisabet I.,1973-Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Farmakometri
(author)
Can a pharmacokinetic/pharmacodynamic (PKPD) model be predictive across bacterial densities and strains? : External evaluation of a PKPD model describing longitudinal in vitro data
- Article/chapterEnglish2017
Publisher, publication year, extent ...
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2017-08-17
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OXFORD UNIV PRESS,2017
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-340705
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-340705URI
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https://doi.org/10.1093/jac/dkx269DOI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Background: Pharmacokinetic/pharmacodynamic (PKPD) models developed based on data from in vitro time-kill experiments have been suggested to contribute to more efficient drug development programmes and better dosing strategies for antibiotics. However, for satisfactory predictions such models would have to show good extrapolation properties. Objectives: To evaluate if a previously described mechanism-based PKPD model was able also to predict drug efficacy for higher bacterial densities and across bacterial strains. Methods: A PKPD model describing the efficacy of ciprofloxacin on Escherichia coli was evaluated. The predictive performance of the model was evaluated across several experimental conditions with respect to: (i) bacterial start inoculum ranging from the standard of similar to 10(6) cfu/mL up to late stationary-phase cultures; and (ii) efficacy for seven additional strains (three laboratory and four clinical strains), not included during the model development process, based only on information regarding their MIC. Model predictions were performed according to the intended experimental protocol and later compared with observed bacterial counts. Results: The mechanism-based PKPD model structure developed based on data from standard start inoculum experiments was able to accurately describe the inoculum effect. The model successfully predicted the time course of drug efficacy for additional laboratory and clinical strains based on only the MIC values. The model structure was further developed to better describe the stationary phase data. Conclusions: This study supports the use of mechanism-based PKPD models based on preclinical data for predictions of untested scenarios.
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Khan, David D.Uppsala universitet,Institutionen för farmaceutisk biovetenskap(Swepub:uu)davkh409
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Cao, ShaUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi(Swepub:uu)shaca305
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Lustig, UlrikaUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi(Swepub:uu)ulu03860
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Hughes, Diarmaid,1956-Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi(Swepub:uu)diarhugh
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Andersson, Dan IUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi(Swepub:uu)dan19789
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Friberg, Lena EUppsala universitet,Institutionen för farmaceutisk biovetenskap,Farmakometri(Swepub:uu)lenasimo
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Uppsala universitetInstitutionen för farmaceutisk biovetenskap
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Related titles
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In:Journal of Antimicrobial Chemotherapy: OXFORD UNIV PRESS72:11, s. 3108-31160305-74531460-2091
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