An Interactive Generic Physiologically Based Pharmacokinetic (igPBPK) Modeling Platform to Predict Drug Withdrawal Intervals in Cattle and Swine: A Case Study on Flunixin, Florfenicol, and Penicillin G

Toxicological Sciences - Tập 188 Số 2 - Trang 180-197 - 2022
Wei-Chun Chou1,2, Lisa A. Tell3, Ronald E. Baynes4, Jennifer L. Davis5, Fiona P. Maunsell6, Jim E. Riviere7,4, Zhoumeng Lin1,2
1Center for Environmental and Human Toxicology, University of Florida , Florida 32608, USA
2Department of Environmental and Global Health, College of Public Health and Health Professions, University of Florida , Gainesville, Florida 32610, USA
3Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California-Davis , Davis, California 95616, USA
4Center for Chemical Toxicology Research and Pharmacokinetics, Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University , Raleigh, North Carolina 27606, USA
5Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine , Blacksburg, Virginia 24060, USA
6Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida , Gainesville, Florida 32608, USA
71Data Consortium, Kansas State University , Olathe, Kansas 66061, USA

Tóm tắt

AbstractViolative chemical residues in edible tissues from food-producing animals are of global public health concern. Great efforts have been made to develop physiologically based pharmacokinetic (PBPK) models for estimating withdrawal intervals (WDIs) for extralabel prescribed drugs in food animals. Existing models are insufficient to address the food safety concern as these models are either limited to 1 specific drug or difficult to be used by non-modelers. This study aimed to develop a user-friendly generic PBPK platform that can predict tissue residues and estimate WDIs for multiple drugs including flunixin, florfenicol, and penicillin G in cattle and swine. Mechanism-based in silico methods were used to predict tissue/plasma partition coefficients and the models were calibrated and evaluated with pharmacokinetic data from Food Animal Residue Avoidance Databank (FARAD). Results showed that model predictions were, in general, within a 2-fold factor of experimental data for all 3 drugs in both species. Following extralabel administration and respective U.S. FDA-approved tolerances, predicted WDIs for both cattle and swine were close to or slightly longer than FDA-approved label withdrawal times (eg, predicted 8, 28, and 7 days vs labeled 4, 28, and 4 days for flunixin, florfenicol, and penicillin G in cattle, respectively). The final model was converted to a web-based interactive generic PBPK platform. This PBPK platform serves as a user-friendly quantitative tool for real-time predictions of WDIs for flunixin, florfenicol, and penicillin G following FDA-approved label or extralabel use in both cattle and swine, and provides a basis for extrapolating to other drugs and species.

Từ khóa


Tài liệu tham khảo

Adams, 1987, Tissue concentrations and pharmacokinetics of florfenicol in male veal calves given repeated doses, Am. J. Vet. Res, 48, 1725

Aksu, 2017, Changes in the total lipid, neutral lipid, phospholipid and fatty acid composition of phospholipid fractions during pastirma processing, a dry-cured meat product, Korean J. Food Sci. Anim. Resour, 37, 18, 10.5851/kosfa.2017.37.1.18

Baron, 2015, Simulation from ODE-based population PK/PD and systems pharmacology models in R with mrgsolve, J. Pharmacokinet. Phar, 42, S84

Bates, 2020, A study to assess the correlation between plasma, oral fluid and urine concentrations of flunixin meglumine with the tissue residue depletion profile in finishing-age swine, BMC Vet. Res, 16, 211, 10.1186/s12917-020-02429-w

Baynes, 2016, Health concerns and management of select veterinary drug residues, Food Chem. Toxicol, 88, 112, 10.1016/j.fct.2015.12.020

Berezhkovskiy, 2004, Volume of distribution at steady state for a linear pharmacokinetic system with peripheral elimination, J. Pharm. Sci, 93, 1628, 10.1002/jps.20073

Bretzlaff, 1987, Florfenicol in non-lactating dairy cows: Pharmacokinetics, binding to plasma proteins, and effects on phagocytosis by blood neutrophils, J. Vet. Pharmacol. Ther, 10, 233, 10.1111/j.1365-2885.1987.tb00534.x

Buur, 2006, Pharmacokinetics of flunixin meglumine in swine after intravenous dosing, J. Vet. Pharmacol. Ther, 29, 437, 10.1111/j.1365-2885.2006.00788.x

Canton, 2021, Rational pharmacotherapy in infectious diseases: Issues related to drug residues in edible animal tissues, Animals (Basel, 11, 2878, 10.3390/ani11102878

Chiesa, 2006, Bovine kidney tissue/biological fluid correlation for penicillin, J. Vet. Pharmacol. Ther, 29, 299, 10.1111/j.1365-2885.2006.00747.x

Chou, 2019, Bayesian evaluation of a physiologically based pharmacokinetic (PBPK) model for perfluorooctane sulfonate (PFOS) to characterize the interspecies uncertainty between mice, rats, monkeys, and humans: Development and performance verification, Environ. Int, 129, 408, 10.1016/j.envint.2019.03.058

Chou, 2020, Probabilistic human health risk assessment of perfluorooctane sulfonate (PFOS) by integrating in vitro, in vivo toxicity, and human epidemiological studies using a Bayesian-based dose-response assessment coupled with physiologically based pharmacokinetic (PBPK) modeling approach, Environ. Int, 137, 10.1016/j.envint.2020.105581

Chou, 2021, Development of a gestational and lactational physiologically based pharmacokinetic (PBPK) model for perfluorooctane sulfonate (PFOS) in rats and humans and its implications in the derivation of health-based toxicity values, Environ. Health Persp, 129, 37004, 10.1289/EHP7671

Croubels, 2006, Pharmacokinetics and oral bioavailability of florfenicol in veal calves, J. Vet. Pharmacol. Ther, 29, 104

Cully, 2014, Public health the politics of antibiotics, Nature, 509, S16, 10.1038/509S16a

de Craene, 1997, Pharmacokinetics of florfenicol in cerebrospinal fluid and plasma of calves, Antimicrob. Agents Chemother, 41, 1991, 10.1128/AAC.41.9.1991

Djebala, 2021, Description of plasma penicillin G concentrations after intramuscular injection in double-muscled cows to optimize the timing of antibiotherapy for caesarean section, Vet. Sci, 8, 67, 10.3390/vetsci8050067

Durso, 2014, Impacts of antibiotic use in agriculture: What are the benefits and risks?, Curr. Opin. Microbiol, 19, 37, 10.1016/j.mib.2014.05.019

1999

Embrechts, 2013, The influence of the galenic form on pharmacokinetics of florfenicol after intramuscular administration in pigs, J. Vet. Pharmacol. Ther, 36, 92, 10.1111/j.1365-2885.2012.01387.x

1998

2005

2018

2020

Galbraith, 1996, Protein binding and in vitro serum thromboxane B2 inhibition by flunixin meglumine and meclofenamic acid in dog, goat and horse blood, Res. Vet. Sci, 61, 78, 10.1016/S0034-5288(96)90115-0

Gilliam, 2008, Pharmacokinetics of florfenicol in serum and synovial fluid after regional intravenous perfusion in the distal portion of the hind limb of adult cows, Am. J. Vet. Res, 69, 997, 10.2460/ajvr.69.8.997

Halleran, 2022, Update on withdrawal intervals following extralabel use of procaine penicillin G in cattle and swine, J. Am. Vet. Med. Assoc, 260, 50, 10.2460/javma.21.05.0268

Haritova, 2010, A simulation model for the prediction of tissue: Plasma partition coefficients for drug residues in natural casings, Vet. J, 185, 278, 10.1016/j.tvjl.2009.06.007

Henri, 2017, A physiologically based pharmacokinetic model for chickens exposed to feed supplemented with monensin during their lifetime, J. Vet. Pharmacol. Ther, 40, 370, 10.1111/jvp.12370

Howard, 2014, The effect of breed and sex on sulfamethazine, enrofloxacin, fenbendazole and flunixin meglumine pharmacokinetic parameters in swine, J. Vet. Pharmacol. Ther, 37, 531, 10.1111/jvp.12128

Hsieh, 2018, Applying a global sensitivity analysis workflow to improve the computational efficiencies in physiologically-based pharmacokinetic modeling, Front. Pharmacol, 9, 588, 10.3389/fphar.2018.00588

2009

Jaroszewski, 2008, Pharmacokinetics of flunixin in mature heifers following multiple intravenous administration, Pol. J. Vet. Sci, 11, 199

Jiang, 2006, Pharmacokinetics of florfenicol in pigs following intravenous, intramuscular or oral administration and the effects of feed intake on oral dosing, J. Vet. Pharmacol. Ther, 29, 153, 10.1111/j.1365-2885.2006.00727.x

Kamiya, 2019, Plasma and hepatic concentrations of chemicals after virtual oral administrations extrapolated using rat plasma data and simple physiologically based pharmacokinetic models, Chem. Res. Toxicol, 32, 792, 10.1021/acs.chemrestox.9b00063

Kim, 2008, Comparative pharmacokinetics of tylosin or florfenicol after a single intramuscular administration at two different doses of tylosin-florfenicol combination in pigs, J. Vet. Med. Sci, 70, 99, 10.1292/jvms.70.99

Kissell, 2016, Pharmacokinetics and tissue elimination of flunixin in veal calves, Am. J. Vet. Res, 77, 634, 10.2460/ajvr.77.6.634

Kittrell, 2020, Pharmacokinetics of intravenous, intramuscular, oral, and transdermal administration of flunixin meglumine in pre-wean piglets, Front. Vet. Sci, 7, 586, 10.3389/fvets.2020.00586

Kleinhenz, 2016, The pharmacokinetics of transdermal flunixin meglumine in holstein calves, J. Vet. Pharmacol. Ther, 39, 612, 10.1111/jvp.12314

Korsrud, 1993, Depletion of intramuscularly and subcutaneously injected procaine penicillin G from tissues and plasma of yearling beef steers, Can. J. Vet. Res, 57, 223

Korsrud, 1998, Depletion of penicillin G residues in tissues, plasma and injection sites of market pigs injected intramuscularly with procaine penicillin G, Food Addit. Contam, 15, 421, 10.1080/02652039809374662

KuKanich, 2005, Effect of formulation and route of administration on tissue residues and withdrawal times, J. Am. Vet. Med. Assoc, 227, 1574, 10.2460/javma.2005.227.1574

Lacroix, 2011, Comparative bioavailability between two routes of administration of florfenicol and flunixin in cattle, Rev. Med. Vet, 162, 321

Lautz, 2020, An open source physiologically based kinetic model for the chicken (Gallus gallus domesticus): Calibration and validation for the prediction residues in tissues and eggs, Environ. Int, 136, 105488, 10.1016/j.envint.2020.105488

Law, 1999, Xenobiotics in Fish, 105, 10.1007/978-1-4615-4703-7_8

Lei, 2018, PK–PD integration modeling and cutoff value of florfenicol against Streptococcus suis in pigs, Front. Pharmacol, 9, 2, 10.3389/fphar.2018.00002

Li, 2002, Tissue pharmacokinetics of florfenicol in pigs experimentally infected with Actinobacillus pleuropneumoniae, Eur. J. Drug Metab. Pharmacokinet, 27, 265, 10.1007/BF03192337

Li, 2019, Integration of Food Animal Residue Avoidance Databank (FARAD) empirical methods for drug withdrawal interval determination with a mechanistic population-based interactive physiologically based pharmacokinetic (ipbpk) modeling platform: Example for flunixin meglumine administration, Arch. Toxicol, 93, 1865, 10.1007/s00204-019-02464-z

Li, 2017, Development and application of a population physiologically based pharmacokinetic model for penicillin G in swine and cattle for food safety assessment, Food Chem. Toxicol, 107, 74, 10.1016/j.fct.2017.06.023

Li, 2018, Probabilistic physiologically based pharmacokinetic model for penicillin g in milk from dairy cows following intramammary or intramuscular administrations, Toxicol. Sci, 164, 85, 10.1093/toxsci/kfy067

Li, 2019, An integrated experimental and physiologically based pharmacokinetic modeling study of penicillin G in heavy sows, J. Vet. Pharmacol. Ther, 42, 461, 10.1111/jvp.12766

Li, 2021, Physiological parameter values for physiologically based pharmacokinetic models in food-producing animals. Part III: Sheep and goat, J. Vet. Pharmacol. Ther, 44, 456, 10.1111/jvp.12938

Lin, 2013, Estimation of placental and lactational transfer and tissue distribution of atrazine and its main metabolites in rodent dams, fetuses, and neonates with physiologically based pharmacokinetic modeling, Toxicol. Appl. Pharm, 273, 140, 10.1016/j.taap.2013.08.010

Lin, 2016, Mathematical modeling and simulation in animal health—Part II: Principles, methods, applications, and value of physiologically based pharmacokinetic modeling in veterinary medicine and food safety assessment, J. Vet. Pharmacol. Ther, 39, 421, 10.1111/jvp.12311

Lin, 2017, Performance assessment and translation of physiologically based pharmacokinetic models from acsLX to Berkeley Madonna, MATLAB, and R language: Oxytetracycline and gold nanoparticles as case examples, Toxicol. Sci, 158, 23, 10.1093/toxsci/kfx070

Lin, 2020, 458

Lin, 2020, Physiological parameter values for physiologically based pharmacokinetic models in food-producing animals. Part I: Cattle and swine, J. Vet. Pharmacol. Ther, 43, 385, 10.1111/jvp.12861

Lin, 2015, Development and application of a multiroute physiologically based pharmacokinetic model for oxytetracycline in dogs and humans, J. Pharm. Sci, 104, 233, 10.1002/jps.24244

Lin, 2016, A physiologically based pharmacokinetic model for polyethylene glycol-coated gold nanoparticles of different sizes in adult mice, Nanotoxicology, 10, 162

Liu, 2003, Pharmacokinetics of florfenicol in healthy pigs and in pigs experimentally infected with Actinobacillus pleuropneumoniae, Antimicrob. Agents Chemother, 47, 820, 10.1128/AAC.47.2.820-823.2003

Lobell, 1994, Pharmacokinetics of florfenicol following intravenous and intramuscular doses to cattle, J. Vet. Pharmacol. Ther, 17, 253, 10.1111/j.1365-2885.1994.tb00241.x

Lupton, 2014, Depletion of penicillin G residues in heavy sows after intramuscular injection. Part I: Tissue residue depletion, J. Agric. Food Chem, 62, 7577, 10.1021/jf501492v

McNally, 2011, A workflow for global sensitivity analysis of PBPK models, Front. Pharmacol, 2, 31, 10.3389/fphar.2011.00031

Mirfazaelian, 2006, Development of a physiologically based pharmacokinetic model for deltamethrin in the adult male Sprague-Dawley rat, Toxicol. Sci, 93, 432, 10.1093/toxsci/kfl056

Norbrook Laboratories, 2015

1999, The Use of Drugs in Food Animals: Benefits and Risks, 110

Odensvik, 1995, Pharmacokinetics of flunixin and its effect on prostaglandin-F2-alpha metabolite concentrations after oral and intravenous administration in heifers, J. Vet. Pharmacol. Ther, 18, 254, 10.1111/j.1365-2885.1995.tb00589.x

Odensvik, 1995, High-performance liquid-chromatography method for determination of flunixin in bovine plasma and pharmacokinetics after single and repeated doses of the drug, Am. J. Vet. Res, 56, 489, 10.2460/ajvr.1995.56.04.489

2021

Pairis-Garcia, 2013, Pharmacokinetics of flunixin meglumine in mature swine after intravenous, intramuscular and oral administration, BMC Vet. Res, 9, 165, 10.1186/1746-6148-9-165

Papich, 1993, A study of the disposition of procaine penicillin G in feedlot steers following intramuscular and subcutaneous injection, J. Vet. Pharmacol. Ther, 16, 317, 10.1111/j.1365-2885.1993.tb00178.x

Peterson, 1978, Quantitative binding of penicillin-G to tissue-homogenates as determined with preparative ultra-centrifuge, J. Lab. Clin. Med, 91, 463

Poulin, 2019, Application of the tissue composition-based model to minipig for predicting the volume of distribution at steady state and dermis-to-plasma partition coefficients of drugs used in the physiologically based pharmacokinetics model in dermatology, J. Pharm. Sci, 108, 603, 10.1016/j.xphs.2018.09.001

Poulin, 2002, Prediction of pharmacokinetics prior to in vivo studies. 1. Mechanism-based prediction of volume of distribution, J. Pharm. Sci, 91, 129, 10.1002/jps.10005

Ranheim, 2002, Benzathine penicillin G and procaine penicillin G in piglets: Comparison of intramuscular and subcutaneous injection, Vet. Res. Commun, 26, 459, 10.1023/A:1020590408947

Riad, 2021, Development and application of an interactive physiologically based pharmacokinetic (iPBPK) model to predict oxytetracycline tissue distribution and withdrawal intervals in market-age sheep and goats, Toxicol. Sci, 183, 253, 10.1093/toxsci/kfab095

Riviere, 2017, Guide to farad resources: Historical and future perspectives, J. Am. Vet. Med. Assoc, 250, 1131, 10.2460/javma.250.10.1131

Rodgers, 2005, Physiologically based pharmacokinetic modeling 1: Predicting the tissue distribution of moderate-to-strong bases, J. Pharm. Sci, 94, 1259, 10.1002/jps.20322

Rodgers, 2006, Physiologically based pharmacokinetic modelling 2: Predicting the tissue distribution of acids, very weak bases, neutrals and zwitterions, J. Pharm. Sci, 95, 1238, 10.1002/jps.20502

Schmitt, 2008, General approach for the calculation of tissue to plasma partition coefficients, Toxicol. In Vitro, 22, 457, 10.1016/j.tiv.2007.09.010

Schneckener, 2019, Prediction of oral bioavailability in rats: Transferring insights from in vitro correlations to (deep) machine learning models using in silico model outputs and chemical structure parameters, J. Chem. Inf. Model, 59, 4893, 10.1021/acs.jcim.9b00460

Shelver, 2013, Comparison of ELISA and LC-MS/MS for the measurement of flunixin plasma concentrations in beef cattle after intravenous and subcutaneous administration, J. Agr. Food Chem, 61, 2679, 10.1021/jf304773p

Sidhu, 2014, Pharmacokinetic–pharmacodynamic integration and modelling of florfenicol in calves, J. Vet. Pharmacol. Ther, 37, 231, 10.1111/jvp.12093

Singh, 2020, Artificial intelligence and machine learning in computational nanotoxicology: Unlocking and empowering nanomedicine, Adv. Healthc. Mater, 9, 1901862, 10.1002/adhm.201901862

2002

2006

2008

Tan, 2018, Challenges associated with applying physiologically based pharmacokinetic modeling for public health decision-making, Toxicol. Sci, 162, 341, 10.1093/toxsci/kfy010

Tardiveau, 2022, A physiologically based pharmacokinetic (PBPK) model exploring the blood-milk barrier in lactating species - a case study with oxytetracycline administered to dairy cows and goats, Food Chem. Toxicol, 161, 112848, 10.1016/j.fct.2022.112848

Trolldenier, 1986, Blood-levels, pharmacokinetics, and residualization of benzylpenicillins (Ursopen 100000) in calif, following subcutaneous injection, Monatsh. Veterinarmed, 41, 435

2013

Utsey, 2020, Quantification of the impact of partition coefficient prediction methods on physiologically based pharmacokinetic model output using a standardized tissue composition, Drug Metab. Dispos, 48, 903, 10.1124/dmd.120.090498

Vanselow, 2001, The use of drugs in food animals: Benefits and risks, Aust. J. Agr. Resour. Econ, 45, 641

Varma, 1986, Pharmacokinetics of florfenicol in veal calves, J. Vet. Pharmacol. Ther, 9, 412, 10.1111/j.1365-2885.1986.tb00062.x

Voorspoels, 1999, Pharmacokinetics of florfenicol after treatment of pigs with single oral or intramuscular doses or with medicated feed for three days, Vet. Rec, 145, 397, 10.1136/vr.145.14.397

Wang, 2021, Physiological parameter values for physiologically based pharmacokinetic models in food-producing animals. Part II: Chicken and turkey, J. Vet. Pharmacol. Ther, 44, 423, 10.1111/jvp.12931

2010

Yang, 2019, Development and application of a population physiologically based pharmacokinetic model for florfenicol and its metabolite florfenicol amine in cattle, Food Chem. Toxicol, 126, 285, 10.1016/j.fct.2019.02.029

Yang, 2015, Development of a physiologically based pharmacokinetic model for assessment of human exposure to bisphenol A, Toxicol. Appl. Pharm, 289, 442, 10.1016/j.taap.2015.10.016

Zeng, 2019, Assessing global human exposure to T-2 toxin via poultry meat consumption using a lifetime physiologically based pharmacokinetic model, J. Agric. Food Chem, 67, 1563, 10.1021/acs.jafc.8b07133

Zhang, 2016, Nanoemulsion formulation of florfenicol improves bioavailability in pigs, J. Vet. Pharmacol. Ther, 39, 84, 10.1111/jvp.12230

Zhou, 2021, Apply a physiologically based pharmacokinetic model to promote the development of enrofloxacin granules: Predict withdrawal interval and toxicity dose, Antibiotics (Basel), 10, 955, 10.3390/antibiotics10080955

Thông tin
Thông tin xuất bản

Toxicological Sciences

Tập 188 Số 2

180-197

Thông tin tác giả