An Interactive Generic Physiologically Based Pharmacokinetic (igPBPK) Modeling Platform to Predict Drug Withdrawal Intervals in Cattle and Swine: A Case Study on Flunixin, Florfenicol, and Penicillin G

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dc.contributor.authorChou, Wei-Chunen
dc.contributor.authorTell, Lisa A.en
dc.contributor.authorBaynes, Ronald E.en
dc.contributor.authorDavis, Jennifer L.en
dc.contributor.authorMaunsell, Fiona P.en
dc.contributor.authorRiviere, Jim E.en
dc.contributor.authorLin, Zhoumengen
dc.date.accessioned2024-01-19T13:22:02Zen
dc.date.available2024-01-19T13:22:02Zen
dc.date.issued2022-07-28en
dc.description.abstractViolative chemical residues in edible tissues from food-producing animals are of global public health concern. Great efforts have been made to develop physiologically based pharmacokinetic (PBPK) models for estimating withdrawal intervals (WDIs) for extralabel prescribed drugs in food animals. Existing models are insufficient to address the food safety concern as these models are either limited to 1 specific drug or difficult to be used by non-modelers. This study aimed to develop a user-friendly generic PBPK platform that can predict tissue residues and estimate WDIs for multiple drugs including flunixin, florfenicol, and penicillin G in cattle and swine. Mechanism-based in silico methods were used to predict tissue/plasma partition coefficients and the models were calibrated and evaluated with pharmacokinetic data from Food Animal Residue Avoidance Databank (FARAD). Results showed that model predictions were, in general, within a 2-fold factor of experimental data for all 3 drugs in both species. Following extralabel administration and respective U.S. FDA-approved tolerances, predicted WDIs for both cattle and swine were close to or slightly longer than FDA-approved label withdrawal times (eg, predicted 8, 28, and 7 days vs labeled 4, 28, and 4 days for flunixin, florfenicol, and penicillin G in cattle, respectively). The final model was converted to a web-based interactive generic PBPK platform. This PBPK platform serves as a user-friendly quantitative tool for real-time predictions of WDIs for flunixin, florfenicol, and penicillin G following FDA-approved label or extralabel use in both cattle and swine, and provides a basis for extrapolating to other drugs and species.en
dc.description.versionPublished versionen
dc.format.extentPages 180-197en
dc.format.extent18 page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1093/toxsci/kfac056en
dc.identifier.eissn1096-0929en
dc.identifier.issn1096-6080en
dc.identifier.issue2en
dc.identifier.orcidDavis, Jennifer [0000-0002-7930-4589]en
dc.identifier.other6596615 (PII)en
dc.identifier.pmid35642931en
dc.identifier.urihttps://hdl.handle.net/10919/117404en
dc.identifier.volume188en
dc.language.isoenen
dc.publisherOxford University Pressen
dc.relation.urihttps://www.ncbi.nlm.nih.gov/pubmed/35642931en
dc.rightsCreative Commons Attribution-NonCommercial 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/en
dc.subjectdrug residueen
dc.subjectFood Animal Residue Avoidance Databank (FARAD)en
dc.subjectfood safetyen
dc.subjectinteractive generic physiologically based pharmacokinetic (igPBPK) modelen
dc.subjectwithdrawal interval (WDI)en
dc.subject.meshAnimalsen
dc.subject.meshCattleen
dc.subject.meshSwineen
dc.subject.meshThiamphenicolen
dc.subject.meshPenicillin Gen
dc.subject.meshClonixinen
dc.subject.meshDrugs, Genericen
dc.subject.meshDrug Residuesen
dc.subject.meshModels, Biologicalen
dc.titleAn Interactive Generic Physiologically Based Pharmacokinetic (igPBPK) Modeling Platform to Predict Drug Withdrawal Intervals in Cattle and Swine: A Case Study on Flunixin, Florfenicol, and Penicillin Gen
dc.title.serialToxicological Sciencesen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dc.type.otherJournalen
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Veterinary Medicineen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/Biomedical Sciences and Pathobiologyen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/CVM T&R Facultyen

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