Tissue Deposition and Residue Depletion of Cyadox and Its Three Major Metabolites in Pigs after Oral Administration

Abstract

Tissue deposition and residue depletion profiles of cyadox (Cyx) and its three major metabolites, including 1,4-bisdesoxycyadox (Cy1), 4-desoxycyadox (Cy2), and quinoxaline-2-carboxylic acid (QCA), in pigs after multiple oral administrations were determined. Thirty-five healthy adult pigs were randomly divided into seven groups and orally treated with Cyx at a dosage of 20 mg/kg of body weight for five consecutive days. Each group of five pigs was randomly slaughtered 12, 24, 72, 120, 168, 216, and 264 h after the last dosing, and tissue samples, including muscle, liver, kidney, and fat, were collected and analyzed via the liquid chromatography-tandem mass spectrometry method. The concentration-time data of Cyx and its three metabolites (Cy1, Cy2, and QCA) were analyzed with WinNonlin. Results showed that metabolites of Cyx were quickly generated in swine tissues and the concentrations of QCA in kidney were higher than those of Cyx and other metabolites in all edible tissues. These results provide further insight into the metabolism of Cyx and confirmation of the residue marker and target tissue of Cyx in pigs.

Estimation of residue depletion of cyadox and its marker residue in edible tissues of pigs using physiologically based pharmacokinetic modelling

“…The data used to calibrate the model for CYA and BDCYA are from Li et al (2013). Briefly, thirty-five healthy adult pigs were randomly divided into seven groups and treated with CYA by oral gavage at a dosage of 20 mg/kg for five days.…”

“…Briefly, thirty-five healthy adult pigs were randomly divided into seven groups and treated with CYA by oral gavage at a dosage of 20 mg/kg for five days. Pigs (n=5) were randomly slaughtered at 12, 24, 72, 120, 168, 216, and 264h after the last dosing, and tissue samples (muscle, liver, kidney, and fat) were collected and analyzed for the concentrations of CYA and its metabolites including BDCYA via a liquid chromatography−tandem mass spectrometry method (Li et al, 2013). Model structure.…”

“…Several PBPK models have been developed to predict veterinary drug residues in food animals (Craigmill, 2003;Buur et al, 2006Buur et al, , 2008Cortright et al, 2009; A c c e p t e d M a n u s c r i p t al., 2011; 2014). All of these models successfully simulated the depletion of parent drug, with only two recent models describing the kinetics of their metabolites (Yang et al, 2013;Yang et al, 2015). To date, no single model has linked the disposition of both moieties which is crucial since food safety is estimated from total drug and metabolite exposure, but is then monitored based only on either the parent drug or one metabolite serving as a marker residue.…”

“…Pharmacokinetic and residue depletion of CYA in pigs after oral and dietary exposures TFAC_A_1100330-Page 4 of 48 A c c e p t e d M a n u s c r i p t have been reported (Zhao et al, 2012;Li et al, 2013;Qiu et al, 2012) with CYA and BDCYA depletion being relatively rapid in tissues of pigs. A PBPK model for quinoxaline-2-carboxylic acid (QCA), one of the CYA metabolites was developed in rats and pigs (Yang et al, 2015).…”

Pharmacokinetics of tulathromycin in edible tissues of healthy and experimentally infected pigs withActinobacillus pleuropneumoniae

“…In the most cases pharmacokinetics and the tissue depletion of antibiotics have been studied in healthy animals (Anadón et al 2008;El-Gendi et al 2010;Anadón et al 2011;Anadón et al 2012;Li et al 2013), and influence of infection on the tissue pharmacokinetics is studied very rarely (AgersØ and Friis 1998;Ding et al 2013). …”