Effect of age on the pharmacokinetics and distribution of tulathromycin in interstitial and pulmonary epithelial lining fluid in healthy calves

Mzyk, Danielle A.; Bublitz, Claire M.; Hobgood, Ginger D.; Martinez, Marilyn N.; Smith, Geof W.; Baynes, Ronald E.

doi:10.2460/ajvr.79.11.1193

Cited by 10 publications

(13 citation statements)

References 45 publications

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“…Lipid-soluble drugs such as unixin have high apparent volumes of distribution, and unixin has been shown to be highly bound to plasma proteins in pigs (99% (21)). The body fat-to-water ratio increases with age, resulting in increased sequestration of unixin in adipose tissue (20), which may explain the variation in Vd/F between 6-day-old piglets and the juvenile pigs in the present study, both administered 2.2 mg/kg unixin intramuscularly.…”

Section: Liver and Kidneymentioning

confidence: 65%

“…Only one previous study reported the volume of distribution/F (Vd/F) following an intramuscular dose of unixin, and the reported value was much less than the Vd/F in the present study (0.92 L/kg for 6-day-old piglets (18) compared to 2.88 L/kg in this study). The Vd/F is affected by the bioavailability (F) and the degree of plasma and tissue protein binding, as well as the drug's lipophilicity (20). Lipid-soluble drugs such as unixin have high apparent volumes of distribution, and unixin has been shown to be highly bound to plasma proteins in pigs (99% (21)).…”

Section: Liver and Kidneymentioning

confidence: 99%

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Plasma, Urine and Tissue Concentrations of Flunixin and Meloxicam in Pigs

Nixon

Mays

Routh

et al. 2020

Preprint

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Background: The objective of this study was to determine the renal clearance of flunixin and meloxicam in pigs and compare plasma and urine concentrations and tissue residues of these drugs. Urine clearance is important for livestock show animals where urine is routinely tested for these drugs. Fourteen Yorkshire/Landrace cross pigs were housed in individual metabolism cages to facilitate urine collection. This is a unique feature of this study compared to other reports. Animals into received either 2.2 mg/kg flunixin or 0.4 mg/kg meloxicam via intramuscular injection and samples analyzed by mass spectrometry. Pigs were euthanized when drugs were no longer detected in urine and liver and kidneys were collected to quantify residues.Results: Drug levels in urine reached peak concentrations between 4 and 8 h post-dose for both flunixin and meloxicam. Flunixin urine concentrations were higher than maximum levels in plasma. Urine concentrations for flunixin and meloxicam were last detected above the limit of quantification at 120 h and 48 h, respectively. The renal clearance of flunixin and meloxicam was 4.72 ± 2.98 mL/h/kg and 0.16 ± 0.04 mL/h/kg, respectively. Mean apparent elimination half-life in plasma was 5.00 ± 1.89 h and 3.22 ± 1.52 h for flunixin and meloxicam, respectively. Six of seven pigs had detectable liver concentrations of flunixin (range 0.0001-0.0012 μg/g) following negative urine samples at 96 and 168 h, however all samples at 168 h were below the FDA tolerance level (0.03 μg/g). Meloxicam was detected in a single liver sample (0.0054 μg/g) at 72 h but was below the EU MRL (0.065 μg/g). Conclusions: These data suggest that pigs given a single intramuscular dose of meloxicam at 0.4 mg/kg or flunixin at 2.2 mg/kg are likely to have detectable levels of the parent drug in urine up to 2 days and 5 days, respectively, after the first dose, but unlikely to have tissue residues above the US FDA tolerance or EU MRL following negative urine testing. This information will assist veterinarians in the therapeutic use of these drugs prior to livestock shows and also inform livestock show authorities involved in testing for these substances.

show abstract

Section: Liver and Kidneymentioning

confidence: 65%

Section: Liver and Kidneymentioning

confidence: 99%

Plasma, Urine and Tissue Concentrations of Flunixin and Meloxicam in Pigs

Nixon

Mays

Routh

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Lipid-soluble drugs such as flunixin have high apparent volumes of distribution, and flunixin has been shown to be highly bound to plasma proteins in pigs (99% (21)). The body fat-to-water ratio increases with age, resulting in increased sequestration of flunixin in adipose tissue(20), which may explain the variation in Vd/F between 6-day-old piglets and the juvenile pigs in the present study, both administered 2.2 mg/kg flunixin intramuscularly. The current Vd/F is also greater than previously reported Vd following IV doses in 10-day-old piglets (0.25 L/kg and 0.26 L/kg, (19)), juvenile pigs (18-27 kg body weight) following IV dose (1.83 L/kg, (21)) and mature sows (0.91 L/kg; (17)).…”

mentioning

confidence: 69%

“…Only one previous study reported the volume of distribution/F following an intramuscular dose of flunixin, and the reported value was much less than the Vd/F in the present study (0.92 L/kg for 6day-old piglets (18) compared to 3.13 L/kg in this study). The Vd/F is affected by the degree of plasma and tissue protein binding, as well as the drug's lipophilicity(20). Lipid-soluble drugs such as flunixin have high apparent volumes of distribution, and flunixin has been shown to be highly bound to plasma proteins in pigs (99% (21)).…”

mentioning

confidence: 99%

Plasma, Urine and Tissue Concentrations of Flunixin and Meloxicam in Pigs

Nixon

Mays

Routh

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: The objective of this study was to compare plasma and urine concentrations of flunixin and meloxicam in pigs, in order to determine urine withdrawal intervals for animals at livestock shows where urine is routinely tested for these drugs. Fourteen Yorkshire/Landrace cross pigs were housed in individual metabolism cages to facilitate complete urine collection. All animals were randomly divided into one of two treatment groups and received either 2.2 mg/kg flunixin or 0.4 mg/kg meloxicam via intramuscular injection. Plasma and urine were collected and analyzed by UPLC-MS/MS. Pigs were humanely euthanized when meloxicam/flunixin could no longer be detected in two consecutive urine samples, and liver and kidneys were collected to quantify any potential residues.Results: Drug levels in urine reached peak concentrations between 4 and 8 h post-dose for both flunixin and meloxicam. Flunixin urine concentrations were higher than maximum levels determined in plasma. Urine concentrations for flunixin and meloxicam were last detected above the limit of quantification (LOQ) at 120 h (0.0005 μg/mL) and 48 h (0.001 μg/mL), respectively. Mean apparent elimination half-life in plasma was 5.00 ± 1.89 h and 3.22 ± 1.52 h for flunixin and meloxicam, respectively. Six of seven pigs had detectable liver concentrations of flunixin (range 0.0001-0.0012 μg/g) following negative urine samples at 96 and 168 h, however all samples at 168 h were below the FDA tolerance level (0.03 μg/g). Meloxicam was detected in a single liver sample at necropsy (0.0054 μg/g) at 72 h but was below the EU MRL (0.065 μg/g) which was used to determine a safety level when FDA tolerance or FSIS testing limits were not established. Urine concentrations did not relate to liver residues at the single slaughter time Conclusions: This data suggests that pigs given a single intramuscular dose of meloxicam at 0.4 mg/kg or flunixin at 2.2 mg/kg are unlikely to have tissue residues above the US FDA tolerance or EU MRL following negative urine testing. This information will assist in generating withdrawal intervals for these NSAIDs for show pigs that might undergo a urine test by the livestock show authorities.

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“…Only one previous study reported the volume of distribution/F (Vd/F) following an intramuscular dose of flunixin, and the reported value was much less than the Vd/F in the present study (0.92 L/kg for 6-day-old piglets [18] compared to 2.88 L/kg in this study). The Vd/F is affected by the bioavailability (F) and the degree of plasma and tissue protein binding, as well as the drug's lipophilicity [20]. Lipid-soluble drugs such as flunixin have high apparent volumes of distribution, and flunixin has been shown to be highly bound to plasma proteins in pigs (99% [21]).…”

Section: Plasma Pharmacokineticsmentioning

confidence: 99%

Plasma, urine and tissue concentrations of Flunixin and Meloxicam in Pigs

et al. 2020

Self Cite

View full text Add to dashboard Cite

Background The objective of this study was to determine the renal clearance of flunixin and meloxicam in pigs and compare plasma and urine concentrations and tissue residues. Urine clearance is important for livestock show animals where urine is routinely tested for these drugs. Fourteen Yorkshire/Landrace cross pigs were housed in individual metabolism cages to facilitate urine collection. This is a unique feature of this study compared to other reports. Animals received either 2.2 mg/kg flunixin or 0.4 mg/kg meloxicam via intramuscular injection and samples analyzed by mass spectrometry. Pigs were euthanized when drugs were no longer detected in urine and liver and kidneys were collected to quantify residues. Results Drug levels in urine reached peak concentrations between 4 and 8 h post-dose for both flunixin and meloxicam. Flunixin urine concentrations were higher than maximum levels in plasma. Urine concentrations for flunixin and meloxicam were last detected above the limit of quantification at 120 h and 48 h, respectively. The renal clearance of flunixin and meloxicam was 4.72 ± 2.98 mL/h/kg and 0.16 ± 0.04 mL/h/kg, respectively. Mean apparent elimination half-life in plasma was 5.00 ± 1.89 h and 3.22 ± 1.52 h for flunixin and meloxicam, respectively. Six of seven pigs had detectable liver concentrations of flunixin (range 0.0001–0.0012 µg/g) following negative urine samples at 96 and 168 h, however all samples at 168 h were below the FDA tolerance level (0.03 µg/g). Meloxicam was detected in a single liver sample (0.0054 µg/g) at 72 h but was below the EU MRL (0.065 µg/g). Conclusions These data suggest that pigs given a single intramuscular dose of meloxicam at 0.4 mg/kg or flunixin at 2.2 mg/kg are likely to have detectable levels of the parent drug in urine up to 2 days and 5 days, respectively, after the first dose, but unlikely to have tissue residues above the US FDA tolerance or EU MRL following negative urine testing. This information will assist veterinarians in the therapeutic use of these drugs prior to livestock shows and also inform livestock show authorities involved in testing for these substances.

show abstract

Effect of age on the pharmacokinetics and distribution of tulathromycin in interstitial and pulmonary epithelial lining fluid in healthy calves

Cited by 10 publications

References 45 publications

Plasma, Urine and Tissue Concentrations of Flunixin and Meloxicam in Pigs

Plasma, Urine and Tissue Concentrations of Flunixin and Meloxicam in Pigs

Plasma, Urine and Tissue Concentrations of Flunixin and Meloxicam in Pigs

Plasma, urine and tissue concentrations of Flunixin and Meloxicam in Pigs

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