Safety evaluation of tulathromycin use in the caprine species: tulathromycin toxicity assessment in goats

Clothier, Kristin A.; Jordan, Dianna M.; Loynachan, Alan T.; Griffith, Ronald W.

doi:10.1111/j.1365-2885.2010.01178.x

Cited by 7 publications

(3 citation statements)

References 10 publications

(12 reference statements)

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“…Tulathromycin has high killing efficacy for caprine respiratory pathogens (Clothier et al ., ) and is a treatment option for caseous lymphadenitis (Washburn et al ., ). When administered to adult goats, it is clinically safe (Washburn et al ., ), and no adverse reactions occurred when administered to neonatal dairy and meat goats at 1×, 3×, and 5× the cattle label dose (Clothier et al ., ). Tissue penetration following single and multiple subcutaneous injections of tulathromycin has been evaluated in juvenile and market‐age goats (Young et al ., ; Clothier et al ., ,b), and two studies (Clothier et al ., ,b) concluded that tissue distribution is similar to that for cattle and swine.…”

Section: Noncompartmental Pharmacokinetic Parameters Calculated From mentioning

confidence: 97%

Pharmacokinetics of tulathromycin in plasma and milk samples after a single subcutaneous injection in lactating goats (Capra hircus)

Grismer

Rowe

Carlson

et al. 2013

Vet Pharm & Therapeutics

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Eight adult female dairy goats received one subcutaneous administration of tulathromycin at a dosage of 2.5 mg/kg body weight. Blood and milk samples were assayed for tulathromycin and the common fragment of tulathromycin, respectively, using liquid chromatography/mass spectrometry. Pharmacokinetic disposition of tulathromycin was analyzed by a noncompartmental approach. Mean plasma pharmacokinetic parameters (±SD) following single-dose administration of tulathromycin were as follows: C(max) (121.54 ± 19.01 ng/mL); T(max) (12 ± 12-24 h); area under the curve AUC(0→∞) (8324.54 ± 1706.56 ng·h/mL); terminal-phase rate constant λz (0.01 ± 0.002 h⁻¹); and terminal-phase rate constant half-life t1/2λz (67.20 h; harmonic). Mean milk pharmacokinetic parameters (±SD) following 45 days of sampling were as follows: Cmax (1594 ± 379.23 ng/mL); Tmax (12 ± 12-36 h); AUC(0→∞) (72,250.51 ± 18,909.57 ng·h/mL); λz (0.005 ± 0.001 h⁻¹); and t(1/2λz) (155.28 h; harmonic). All goats had injection-site reactions that diminished in size over time. The conclusions from this study were that tulathromycin residues are detectable in milk samples from adult goats for at least 45 days following subcutaneous administration, this therapeutic option should be reserved for cases where other treatment options have failed, and goat milk should be withheld from the human food chain for at least 45 days following tulathromycin administration.

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Section: Noncompartmental Pharmacokinetic Parameters Calculated From mentioning

confidence: 97%

Pharmacokinetics of tulathromycin in plasma and milk samples after a single subcutaneous injection in lactating goats (Capra hircus)

Grismer

Rowe

Carlson

et al. 2013

Vet Pharm & Therapeutics

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“…3,4 It has been recommended for use in goats for treatment of various diseases, including pneumonia and caseous lymphadenitis. 5,6 Tulathromycin has been shown to be safe for use in goats, 5,7 and data on pharmacokinetics of the drug in plasma have been published. 8,9 However, pharmacokinetic data regarding the elimination of tulathromycin from tissues are lacking, and this information is necessary to determine appropriate slaughter withdrawal intervals.…”

Section: Pharmacokinetics and Tissue Elimination Of Tulathromycin Fol...mentioning

confidence: 99%

Pharmacokinetics and tissue elimination of tulathromycin following subcutaneous administration in meat goats

Romanet¹,

Smith²,

Leavens³

et al. 2012

ajvr

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“…Tulathromycin is a widely used long-acting triamilide antibiotic labeled for treating respiratory diseases in cattle and swine, and also commonly used in goats in an extra-label manner because it is highly effective against caprine respiratory pathogens [3] and is clinically safe when administered to neonatal dairy and meat goats at 1X, 3X, and 5X the cattle label dose [4]. In the US and Europe, there is no established milk tolerance (equivalent to maximum residue level in Europe) for tulathromycin in goats, thus any detectable residues are considered violative.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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BackgroundExtra-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.ResultsAll 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.ConclusionsThe 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12917-016-0884-4) contains supplementary material, which is available to authorized users.

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Safety evaluation of tulathromycin use in the caprine species: tulathromycin toxicity assessment in goats

Cited by 7 publications

References 10 publications

Pharmacokinetics of tulathromycin in plasma and milk samples after a single subcutaneous injection in lactating goats (Capra hircus)

Pharmacokinetics of tulathromycin in plasma and milk samples after a single subcutaneous injection in lactating goats (Capra hircus)

Pharmacokinetics and tissue elimination of tulathromycin following subcutaneous administration in meat goats

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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