Pharmacokinetics And Residue Depletion Of Cyadox In Swine

Cyadox(Ciadox) is one of derivatives of quinoxaline - N-dioxide. It can be used as a growth promoter and chemotherapeutic agent for swine, calves, poultry and fish. Quinoxaline - N-dioxide could extensively metabolized to several kinds of metabolites in aminal body. In this study, several HPLC methods had been developed for the determination of cyadox and two kinds of its main metabolites in swine samples. Pharmacokinetics and residue depletion in edible tissues of cyadox were studied in swine. This work is to reveal the major metabolites and biotransformation pathways, and the absorption and excretion of cyadox in swine, further to determine the marker residue and target tissue, and to estimate a withdrawal time of cyadox for swine after in-feed administration, and meanwhile to establish the method which can be used to control its residue in edible tissues.According to the analytical methodology in biological samples, several methods had been developed as following: HPLC determination of cyadox and desoxycyadox in swine plasma and edible tissues; HPLC and TLC determination of cyadox and desoxycyadox in swine fece; HPLC and TLC determination of quinoxaline-2-carboxylic acid in swine urine; HPLC determination of quinoxaline-2-carboxylic acid in swine edible tissues. Average recoveries, detection limit and relative standard deviation were studied. Calibration curves were established for measured verious samples. Pharmacokinetics of cyadox in swine were studied after IV and oral administration. In swine receiving a dose of 1 mg/kg bw, only parent cyadoxwas found in plasma. The concentration versus times was fitted with three compartment. The t1h of the distribution phase was 0.02±0. Olh, The t* of the terminal elimination was 1.1 ± 0.3 h. Cyadox was widely distributed in swine, its Vc and Vd was 0. 70±0. 18 L/kg and 4. 5 ± 1. 9L/kg respectively. The AUC was 0. 37±0. 10μ g /ml. h, and the CL was 2. 9±0. 6 L/kg. h. After oral administration of cyadox at dose of 40 mg/kg bw, concentrations of cyadox in swine plasma were very low( < 0.1μg/ml), its AUC was 0. 27±0. 14μg/ml. h, and the bioavailability was 2. 0%±1.4%. Desoxycyadox, the first metabolite of cyadox could been found in plasma after oral administration. Tmax and Cmax of this metabolite was 6. 3±1. 2h and 0. 29±0. 15μ g/ml respectively, and the bioavailability was 8%±5%. Another metabolite was also detected in plasma, it maybe was cyadox monoxide.Piglets were fed a diet specified to contain 25~100 g/lOOOkg cyadox ad libitum for a four months period, cyadox and desoxycyadox levels in plasma 3 hours after administration were below detection limit (0.01 and 0.02μg/ml respectively). Piglets were maintained on cyadox treated ration (25~ 100 g/lOOOkg finished feed) for 1, 2, 3 and 4 months respectively, cyadox and desoxycyadox levels in liver, kindey and muscule were below detection limit (0. 025μg/g) 24 hours after withdrawal of the ration. This result showed that the levels of cyadox and its frist metabolite did'nt gradually increase after long period in-feed administration.Metabolic studies of cyadox in swine were investigated by assay of plasma, urine, fece, liver, kidney and muscle samples after iv, oral and in-feed administration. Cyadox, desoxycyadox and quinoxaline- 2-carboxylic acid were identified by HPLC and TLC assay. Two kinds of additional metabolites were found in plasma and fece after oral administration respectively. They maybe were cyadox monoxide and minor metabolite of side chain. Biotransformation pathways elucidated for cyadox was as following: Reduction of the N-oxide groups and desoxycyadox was obtained, desoxycyadox further metabolized to quinoxaline-2-carboxylic acid(QCA), and thenexcreted from urine as conjugation of QCA.Urinary and fecal excretion of cyadox in swine was investigated after oral administration of a single dose of 40 mg/kg bw. Urine and fece samples were collected by metabolic cages. Cyadox and its metabolites were isolated from samples by thin-layer chromatography (TLC) and compared with...