A physiologically based pharmacokinetic model for the prediction of the depletion of methyl‐3‐quinoxaline‐2‐carboxylic acid, the marker residue of olaquindox, in the edible tissues of pigs

Yang, Bing; Huang, Lingli; Fang, Ke; Wang, Y. L.; Peng, Dengfeng; Liu, Z. L.; Yuang, Z. H.

doi:10.1111/jvp.12053

Cited by 18 publications

(23 citation statements)

References 26 publications

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“…This may be possibly related to the gradual dilution of antibiotics in the gut, which led to the weakened effects. Pharmacokinetic analysis of olaquindox (Yang B. et al, 2014), oxytetracycline (Mevius et al, 1986), kitasamycin (Sun et al, 2010) showed that all these antibiotics could be absorbed by pig gut after oral administration. The abundances of bacteria such as Clostridium , Bacillus , and Sharpea were consistently decreased in the lumen of stomach, duodenum, and jejunum.…”

Section: Discussionmentioning

confidence: 99%

Differences in Microbiota Membership along the Gastrointestinal Tract of Piglets and Their Differential Alterations Following an Early-Life Antibiotic Intervention

Yang

et al. 2017

Front. Microbiol.

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Early-life antibiotic interventions can change the predisposition to disease by disturbing the gut microbiota. However, the impact of antibiotics on gut microbiota in the gastrointestinal tract is not completely understood, although antibiotic-induced alterations in the distal gut have been reported. Here, employing a piglet model, the microbial composition was analyzed by high-throughput 16S rRNA gene sequencing and PICRUSt predictions of metagenome function. The present study showed clear spatial variation of microbial communities in the stomach and intestine, and found that the administration of antibiotics (a mixture of olaquindox, oxytetracycline calcium, kitasamycin) in early life caused markedly differential alterations in the compartmentalized microbiota, with major alterations in their spatial variation in the lumen of the stomach and small intestine. In piglets fed an antibiotic-free diet, most of the variation in microbial communities was concentrated in gut segments and niches (lumen/mucosa). The microbial diversity was higher in the lumen of stomach and duodenum than that in ileum. The early-life antibiotic intervention decreased the abundance of some Lactobacillus species and increased the abundance of potentially pathogenic Streptococcus suis in the lumen of the stomach and small intestine. Interestingly, the intervention increased the abundance of Treponema only in the colonic lumen and that of Faecalibacterium only in the ileal mucosa. Furthermore, the antibiotic intervention exerted location-specific effects on the functional potential involved in the phosphotransferase system (decreased sucrose phosphotransferase in the stomach) and antibiotic-resistance genes (increased in the colon). These results point to an early-life antibiotic-induced dramatic and location-specific shift in the gut microbiota, with profound impact in the foregut and less impact in the hindgut. Collectively, these findings provide new insights into the membership of the microbiota along the gastrointestinal tract of piglets and highlight the importance of considering the foregut microbiota in health management of piglets at early life.

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Section: Discussionmentioning

confidence: 99%

Differences in Microbiota Membership along the Gastrointestinal Tract of Piglets and Their Differential Alterations Following an Early-Life Antibiotic Intervention

Yang

et al. 2017

Front. Microbiol.

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“…Comparison of predicted (lines) and experimentally determined (points) quinoxaline‐2‐carboxylic acid (QCA) residue concentrations in pig liver, kidney, muscle, and adipose (the chemical‐specific parameters are MQCA values from reference) (Yang et al ., ).…”

Section: Resultsmentioning

confidence: 97%

“…They were adjusted slightly for better simulating after the values of other specific chemical parameters were ensured. The same method had been used in other report (Yang et al ., ). The partition coefficients of QCA changed scarcely, and the one of CYX was a little higher than the initial value in Table .…”

Section: Discussionmentioning

confidence: 99%

A physiologically based pharmacokinetic model for quinoxaline‐2‐carboxylic acid in rats, extrapolation to pigs

Yang

Zhou

et al. 2014

Vet Pharm & Therapeutics

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A multi-compartment physiologically based pharmacokinetic (PBPK) model to describe the disposition of cyadox (CYX) and its metabolite quinoxaline-2-carboxylic acid (QCA) after a single oral administration was developed in rats (200 mg/kg b.w. of CYX). Considering interspecies differences in physiology and physiochemistry, the model efficiency was validated by pharmacokinetic data set in swine. The model included six compartments that were blood, muscle, liver, kidney, adipose, and a combined compartment for the rest of tissues. The model was parameterized using rat plasma and tissue concentration data that were generated from this study. Model simulations were achieved using a commercially available software program (ACSLXL ibero version 3.0.2.1). Results supported the validity of the model with simulated tissue concentrations within the range of the observations. The correlation coefficients of the predicted and experimentally determined values for plasma, liver, kidney, adipose, and muscles in rats were 0.98, 0.98, 0.98, 0.99, and 0.95, respectively. The rat model parameters were then extrapolated to pigs to estimate QCA disposition in tissues and validated by tissue concentration of QCA in swine. The correlation coefficients between the predicted and observed values were over 0.90. This model could provide a foundation for developing more reliable pig models once more data are available.

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“…In the last decade, PBPK modeling has been widely used in the area of veterinary medicine, from the prediction of drug tissue residues (Huang et al, ; Leavens et al, ; Yang et al, ), estimating the withdrawal time (Buur, Baynes, Smith, & Riviere, ; Yang, Huang, et al, ; Yang, Zhou, et al, ), to facilitating the food safety assessment (Henri, Carrez, Meda, Laurentie, & Sanders, ; Lin, Gehring, Mochel, Lavé, & Riviere, ; Yang, Huang, et al, ; Yang, Zhou, et al, ). In this study, a PBPK model was established for heavy sows based on a previous generic PBPK model for swine and cattle (Li et al, ).…”

Section: Discussionmentioning

confidence: 99%

“…The population PBPK model can be a useful tool to predict the tissue concentrations and withdrawal intervals following extralabel use of veterinary drugs (Henri et al, ; Lin, Gehring, et al, ; Yang, Huang, et al, ; Yang, Yang, et al, ). The current model provides a conservative estimation of extended withdrawal intervals based on all available pharmacokinetic data of penicillin G in heavy sows and significantly extends label‐recommended withdrawal periods.…”

Section: Discussionmentioning

confidence: 99%

An integrated experimental and physiologically based pharmacokinetic modeling study of penicillin G in heavy sows

Mainquist-Whigham

Karriker

et al. 2019

Vet Pharm & Therapeutics

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Penicillin G is widely used in food‐producing animals at extralabel doses and is one of the most frequently identified violative drug residues in animal‐derived food products. In this study, the plasma pharmacokinetics and tissue residue depletion of penicillin G in heavy sows after repeated intramuscular administrations at label (6.5 mg/kg) and 5 × label (32.5 mg/kg) doses were determined. Plasma, urine, and environmental samples were tested as potential antemortem markers for penicillin G residues. The collected new data and other available data from the literature were used to develop a population physiologically based pharmacokinetic (PBPK) model for penicillin G in heavy sows. The results showed that antemortem testing of urine provided potential correlation with tissue residue levels. Based on the United States Department of Agriculture Food Safety and Inspection Service action limit of 25 ng/g, the model estimated a withdrawal interval of 38 days for penicillin G in heavy sows after 3 repeated intramuscular injections at 5 × label dose. This study improves our understanding of penicillin G pharmacokinetics and tissue residue depletion in heavy sows and provides a tool to predict proper withdrawal intervals after extralabel use of penicillin G in heavy sows, thereby helping safety assessment of sow‐derived meat products.

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A physiologically based pharmacokinetic model for the prediction of the depletion of methyl‐3‐quinoxaline‐2‐carboxylic acid, the marker residue of olaquindox, in the edible tissues of pigs

Cited by 18 publications

References 26 publications

Differences in Microbiota Membership along the Gastrointestinal Tract of Piglets and Their Differential Alterations Following an Early-Life Antibiotic Intervention

Differences in Microbiota Membership along the Gastrointestinal Tract of Piglets and Their Differential Alterations Following an Early-Life Antibiotic Intervention

A physiologically based pharmacokinetic model for quinoxaline‐2‐carboxylic acid in rats, extrapolation to pigs

An integrated experimental and physiologically based pharmacokinetic modeling study of penicillin G in heavy sows

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