Estimation of tulathromycin depletion in plasma and milk after subcutaneous injection in lactating goats using a nonlinear mixed-effects pharmacokinetic modeling approach

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dc.contributor.author Lin, Zhoumeng
dc.contributor.author Cuneo, M.
dc.contributor.author Rowe, J. D.
dc.contributor.author Li, M. J.
dc.contributor.author Tell, L. A.
dc.contributor.author Allison, S.
dc.contributor.author Carlson, J.
dc.contributor.author Riviere, Jim E.
dc.contributor.author Gehring, Ronette
dc.date.accessioned 2017-11-30T21:38:31Z
dc.date.available 2017-11-30T21:38:31Z
dc.identifier.uri http://hdl.handle.net/2097/38287
dc.description Citation: Lin, Z. M., Cuneo, M., Rowe, J. D., Li, M. J., Tell, L. A., Allison, S., . . . Gehring, R. (2016). Estimation of tulathromycin depletion in plasma and milk after subcutaneous injection in lactating goats using a nonlinear mixed-effects pharmacokinetic modeling approach. Bmc Veterinary Research, 12, 10. doi:10.1186/s12917-016-0884-4
dc.description.abstract Background: Extra-label use of tulathromycin in lactating goats is common and may cause violative residues in milk. The objective of this study was to develop a nonlinear mixed-effects pharmacokinetic (NLME-PK) model to estimate tulathromycin depletion in plasma and milk of lactating goats. Eight lactating goats received two subcutaneous injections of 2.5 mg/kg tulathromycin 7 days apart; blood and milk samples were analyzed for concentrations of tulathromycin and the common fragment of tulathromycin (i.e., the marker residue CP-60,300), respectively, using liquid chromatography mass spectrometry. Based on these new data and related literature data, a NLME-PK compartmental model with first-order absorption and elimination was used to model plasma concentrations and cumulative excreted amount in milk. Monte Carlo simulations with 100 replicates were performed to predict the time when the upper limit of the 95% confidence interval of milk concentrations was below the tolerance. Results: All animals were healthy throughout the study with normal appetite and milk production levels, and with mild-moderate injection-site reactions that diminished by the end of the study. The measured data showed that milk concentrations of the marker residue of tulathromycin were below the limit of detection (LOD = 1.8 ng/ml) 39 days after the second injection. A 2-compartment model with milk as an excretory compartment best described tulathromycin plasma and CP-60,300 milk pharmacokinetic data. The model-predicted data correlated with the measured data very well. The NLME-PK model estimated that tulathromycin plasma concentrations were below LOD (1.2 ng/ml) 43 days after a single injection, and 62 days after the second injection with a 95% confidence. These estimated times are much longer than the current meat withdrawal time recommendation of 18 days for tulathromycin in non-lactating cattle. Conclusions: The results suggest that twice subcutaneous injections of 2.5 mg/kg tulathromycin are a clinically safe extra-label alternative approach for treating pulmonary infections in lactating goats, but a prolonged withdrawal time of at least 39 days after the second injection should be considered to prevent violative residues in milk and any dairy goat being used for meat should have an extended meat withdrawal time.
dc.relation.uri https://doi.org/10.1186/s12917-016-0884-4
dc.rights Attribution 4.0 International (CC BY 4.0)
dc.rights.uri https://creativecommons.org/licenses/by/4.0/
dc.subject Tulathromycin
dc.subject Withdrawal Time
dc.subject Goat
dc.subject Food Safety
dc.subject Nonlinear
dc.subject Mixed-Effects (Nlme) Pharmacokinetic Modeling
dc.title Estimation of tulathromycin depletion in plasma and milk after subcutaneous injection in lactating goats using a nonlinear mixed-effects pharmacokinetic modeling approach
dc.type Article
dc.date.published 2016
dc.citation.doi 10.1186/s12917-016-0884-4
dc.citation.issn 1746-6148
dc.citation.jtitle Bmc Veterinary Research
dc.citation.spage 10
dc.citation.volume 12
dc.contributor.authoreid zhoumeng
dc.contributor.authoreid jriviere
dc.contributor.authoreid rgehring
dc.contributor.kstate Lin, Zhoumeng
dc.contributor.kstate Riviere, Jim E.
dc.contributor.kstate Gehring, Ronette


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