Development of a physiologic-based pharmacokinetic model for estimating sulfamethazine concentrations in swine and application to prediction of violative residues in edible tissues

Buur, Jennifer L.; Baynes, Ronald E.; Craigmill, Arthur L.; Riviere, Jim E.

doi:10.2460/ajvr.2005.66.1686

Cited by 46 publications

(43 citation statements)

References 20 publications

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“…The PBPK model (Fig. 1) used in this research was adapted from a previously published model of sulfamethazine in swine (8). Briefly, the model contains five tissue blocks (adipose, kidney, liver, muscle, and carcass) as well as a plasma compartment for sulfamethazine.…”

Section: Methodsmentioning

confidence: 99%

“…Concentrations were modeled by using standard flow-limited mass balance equations. We refer the reader to the work of Buur et al for detailed information regarding the basic model (8). An oral dosing module consisting of a two-tissue-compartment model that included the stomach and intestine (Fig.…”

Section: Methodsmentioning

confidence: 99%

“…The insensitive parameters and their values are presented in Table 1. Readers are referred to the work of Buur et al for details regarding how these parameters were established (8). Only parameters judged to be sensitive were subject to Monte Carlo analysis.…”

Section: Methodsmentioning

confidence: 99%

“…PBPK models are also used in drug development studies (6). Currently, only a handful of PBPK models have been published for veterinary medicine (7,8,10,11). Our previous work predicted meat withdrawal times after the extralabel use of sulfamethazine intravenously (i.v.)…”

mentioning

confidence: 99%

“…Our previous work predicted meat withdrawal times after the extralabel use of sulfamethazine intravenously (i.v.) in swine for the mean of the population (8). However, sulfamethazine is rarely used as an i.v.…”

mentioning

confidence: 99%

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Use of Probabilistic Modeling within a Physiologically BasedPharmacokinetic Model To Predict Sulfamethazine Residue Withdrawal Times in Edible Tissues in Swine

Buur

Baynes

Smith

et al. 2006

Antimicrob Agents Chemother

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The presence of antimicrobial agents in edible tissues of food-producing animals remains a major public health concern. Probabilistic modeling techniques incorporated into a physiologically based pharmacokinetic (PBPK) model were used to predict the amounts of sulfamethazine residues in edible tissues in swine. A PBPK model for sulfamethazine in swine was adapted to include an oral dosing route. The distributions for sensitive parameters were determined and were used in a Monte Carlo analysis to predict tissue residue times. Validation of the distributions was done by comparison of the results of a Monte Carlo analysis to those obtained with an external data set from the literature and an in vivo pilot study. The model was used to predict the upper limit of the 95% confidence interval of the 99th percentile of the population, as recommended by the U.S. Food and Drug Administration (FDA). The external data set was used to calculate the withdrawal time by using the tolerance limit algorithm designed by FDA. The withdrawal times obtained by both methods were compared to the labeled withdrawal time for the same dose. The Monte Carlo method predicted a withdrawal time of 21 days, based on the amounts of residues in the kidneys. The tolerance limit method applied to the time-limited data set predicted a withdrawal time of 12 days. The existing FDA label withdrawal time is 15 days. PBPK models can incorporate probabilistic modeling techniques that make them useful for prediction of tissue residue times. These models can be used to calculate the parameters required by FDA and explore those conditions where the established withdrawal time may not be sufficient.Sulfamethazine is a sulfonamide antibiotic used in the swine industry as a feed or water additive. It is labeled for the treatment of bacterial pneumonia, cervical abscesses, and bacterial swine enteritis, as well as for the prevention of these diseases during times of stress, maintenance of weight gains in the presence of atrophic rhinitis, growth promotion, and increased feed efficiency (14). Research has shown that high concentrations of this drug may cause thyroid tumors in specific strains of rats (35). Also, a wide range of human allergic reactions are related to sulfonamide drugs in general (37, 43). Thus, there is a large public health concern relating to the possible adverse health effects of consuming sulfamethazine residues found in the edible tissues of swine, warranting the development of predictive pharmacokinetic models.Meat withdrawal periods are required by the U.S. Food and Drug Administration (FDA) to ensure the safety of the meat supply and to address this public health concern. A meat withdrawal period is the time between when a chemotherapeutic is administered to a food animal and the time when that animal is sent to slaughter. These periods are designed to guarantee that the amounts of drug residues in edible tissues will be below tolerance levels before animals are sent to slaughter. Currently, withdrawal times are determined by the toleranc...

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Use of Probabilistic Modeling within a Physiologically BasedPharmacokinetic Model To Predict Sulfamethazine Residue Withdrawal Times in Edible Tissues in Swine

Buur

Baynes

Smith

et al. 2006

Antimicrob Agents Chemother

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Physiological Models

Leavens¹

2011

Comparative Pharmacokinetics

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Pharmacokinetics, Distribution, Bioavailability, and Relationship to Antibiotic Residues

Lees

Toutain

2011

Chemical Analysis of Antibiotic Residues in Food

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Development of a physiologic-based pharmacokinetic model for estimating sulfamethazine concentrations in swine and application to prediction of violative residues in edible tissues

Abstract: Use of this model enabled accurate prediction of sulfamethazine pharmacokinetics in swine and has applications for food safety and prediction of drug residues in edible tissues.

Cited by 46 publications

References 20 publications

Use of Probabilistic Modeling within a Physiologically BasedPharmacokinetic Model To Predict Sulfamethazine Residue Withdrawal Times in Edible Tissues in Swine

Use of Probabilistic Modeling within a Physiologically BasedPharmacokinetic Model To Predict Sulfamethazine Residue Withdrawal Times in Edible Tissues in Swine

Physiological Models

Pharmacokinetics, Distribution, Bioavailability, and Relationship to Antibiotic Residues

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