Pharmacokinetics of cyadox (CYX) and its major metabolites in healthy swine was investigated in this paper. 1,4- Bisdesoxycyadox (BDCYX), cyadox-1-monoxide (CYX-1-O) and quinoxaline-2-carboxylic acid (QCA), three main metabolites of cyadox, were synthesized by College of Science, China Agricultural University. Cyadox (CYX) was administered to 8 healthy cross-bread swine intravenously (i.v.) and orally (p.o.) at a dosage of 1 mg kg-1 body weight and 40 mg kg-1 body weight respectively in a randomized crossover design test with 2-wk washout period. A sensitive high-performance liquid chromatography-tandem mass spectrometry (LC-ESI-MS/MS) method was developed for the determination of cyadox and its major metabolites in plasma. CYX and its major metabolites BDCYX, and CYX-1-O can be detected after intravenous administration of cyadox while CYX and its metabolites BDCYX, CYX-1-O and QCA can be detected after oral administration of CYX. Plasma concentration vs. time profiles of CYX and its major metabolites were analyzed by non-compartmental pharmacokinetic method. Following i.v. administration, the areas under the plasma concentration-time curve (AUC0- ) were (0.38±0.03) μg mL-1 h (CYX), (0.018±0.002) μg mL-1 h (BDCYX) and (0.17±0.02) μg mL-1 h (CYX-1-O), respectively. The terminal elimination half-lives (t1/2lz) were determined to be (0.93±0.07) h (CYX), (1.45±0.04) h (BDCYX), and (0.92±0.04) h (CYX-1-O), respectively. Steady-state distribution volume (Vss) of (2.14±0.11) L kg-1 and total body clearance (CL) of (2.84±0.19) L h-1 kg-1 were determined for CYX after i.v. dosing. The bioavailability (F) of CYX was 2.85% for oral administration. After single i.v. administration, peak plasma concentrations (Cmax) of (1.08±0.06) μg mL-1 (CYX), (0.0068± 0.0004) μg mL-1 (BDCYX) and (0.25±0.03) μg mL-1 (CYX-1-O) were observed at Tmax of 0.033 h (CYX), 1 h (BDCYX) and 0.033 h (CYX-1-O), respectively. The main pharmacokinetic parameters after p.o. administration were as follows: AUC0- were (0.42±0.04) μg mL-1 h (CYX), (1.38±0.14) μg mL-1 h (BDCYX), (0.59±0.02) μg mL-1 h (CYX-1-O) and (1.48±0.09) μg mL-1 h (QCA), respectively. t1/2lz were (4.77±0.33) h (CYX), (5.77±0.56) h (BDCYX), (4.12±0.28) h (CYX-1-O), and (8.51±0.39) h (QCA), respectively. After p.o. administration, Cmaxs of (0.033±0.002) μg mL-1 (CYX), (0.22±0.03) μg mL-1 (BDCYX), (0.089±0.005) μg mL-1 (CYX-1-O), and (0.17± 0.01) μg mL-1 (QCA) were observed at Tmax of (7.38±0.33) h (CYX), (7.25±0.31) h (BDCYX), (7.38±0.33) h (CYX-1-O), and (7.25±0.31) h (QCA), respectively. The results showed that CYX was slowly absorbed after oral administration and most of CYX was transformed to its metabolites in swine. The area under plasma concentration-time curve (AUC0- )of metabolites were higher than that of CYX after p.o. administration, and the elimination half-lives (t1/2lz) of QCA were longer than those of CYX, CYX-1-O, and BDCYX after oral administration.

An accurate and precise method for the determination of tulathromycin in swine plasma was developed and validated. Plasma samples were analyzed by high-performance liquid chromatography with tandem mass spectrometry detection (HPLC-MS/MS) using electrospray ionization (ESI). Tulathromycin was extracted from plasma by precipitation with acetonitrile and separated using a Phenomenex Luna 5 μm C18 column (150 mm×2.0 mm) at a flow rate of 0.25 mL min-1. Solvent A consisted of 0.002 mol L-1 ammonium acetate and formic acid (999:1, v/v), and solvent B was acetonitrile. The mass spectrometer was operated in the selected-ion mode with atmospheric pressure chemical ionization to monitor the respective MH+ ions, namely, m/z 577.3 for tulathromycin and m/z 679.3 for the internal standard roxithromycin. The calibration curves were linear in a dynamic range of 2.0-500 ng mL-1 on the column. The accuracy was ranged from 95.25 to 109.75%, and the precision was ranged from 2.81 to 7.72%. The recoveries measured at 3 concentration levels (20, 250, and 500 ng mL-1) were higher than 98%. The method described above is efficient, and has the required accuracy and precision for rapid determination of tulathromycin in plasma. The method was applied to study the pharmacokinetics of tulathromycin in swine, and tulathromycin demonstrated a rapid absorption, wide distribution, and slow elimination after intramuscular administration.

The pharmacokinetics of quinocetone and its major metabolites in healthy swine was investigated in this paper.Quinocetone was administered to 8 healthy cross-bread swine intravenously and orally at a dosage of 4 and 40 mg kg-1body weight respectively in a randomized crossover design test with two-week washout period. A sensitive highperformanceliquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed for thedetermination of quinocetone and its metabolite 1-desoxyquinocetone in plasma. Plasma concentration versus timeprofiles of quinocetone and its metabolite 1-desoxyquinocetone were analyzed by non-compartmental analysis usingWinnonlin 5.2 software. Mean maximum concentrations (Cmax) for quinocetone was found to be (0.56±0.13) μg mL-1 at 2.92 h,after oral administration of quinocetone. Mean maximum concentrations (Cmax) for 1-desoxyquinocetone after intravenousor oral administration of quinocetone were (0.0095±0.0012) μg mL-1 at 0.083 h and (0.0067±0.0053) μg mL-1 at 3.08 h. Theapparent elimination half-lives (T1/2) for quinocetone and its metabolite 1-desoxyquinocetone were (2.24±0.24) and(5.23±0.56) h after intravenous administration of quinocetone and (2.91±0.29) and (11.85±2.89) h after oral administrationof quinocetone, respectively. Mean areas under the plasma concentration-time curve (AUC0- ) for quinocetone and 1-desoxyquinocetone were (2.02±0.15) and (0.2±0.002) μg h mL-1 respectively after intravenous administration of quinocetone,and (3.5±0.79) and (0.053±0.03) μg h mL-1 after oral administration of quinocetone, respectively. Quinocetone was rapidlyabsorbed and metabolized in swine after oral and intravenous administration. The plasma concentration-time curve(AUC0- ) of 1-desoxyquinocetone were much smaller than those of quinocetone, while the elimination half-lives (T1/2) weremuch longer than those of quinocetone after intravenously (i.v.) or oral administration.

The present study was carried out to investigate the pharmacokinetics of mequindox (MEQ), a new synthetic quinoxaline 1,4-dioxide derivative and its two main metabolites M1 [2-isoethanol mequinoox], M2 [2-isoethanol 1-desoxymequindox] in healthy swine. MEQ (10 mg kg-1 body weight) was administered to nine healthy cross-bread swine via oral, intramuscular, and intravenous routes in a randomized 3×3 crossover design with a 1-wk washout period. A sensitive high-performance liquid chromatography (HPLC) method was used for the determination of plasma concentrations of MEQ and its metabolites M1 and M2. Plasma concentration versus time profiles of MEQ and its metabolites, M1 and M2, were analyzed by noncompartmental analysis using WinNonlin 5.2 software. The mean maximum concentrations (Cmax) of M1 and M2 after intravenous administration of MEQ were (5.27±1.59) μg mL-1 at 1.78 h and (1.01±0.29) μg mL-1 at 0.92 h, respectively. The mean maximum concentrations (Cmax) of MEQ, M1, and M2 were found to be (6.96±3.23), (6.61±1.56), and (0.78 ±0.25) μg mL-1, respectively at 0.15, 1.61, and 1.30 h after intramuscular administration of MEQ, respectively and (0.75±0.45), (6.90±1.52), and (0.62±0.21) μg mL-1, respectively at 0.40, 1.57, and 2.00 h, respectively after oral administration of MEQ. The apparent elimination half-lives (t1/2) of MEQ, M1, and M2 were (0.84±0.35), (7.57±3.93), and (9.56±6.00) h, respectively after intravenous administration of MEQ; (0.50±0.25), (6.30±3.00), and (5.94±2.54) h, respectively after intramuscular administration of MEQ; and (1.64±1.17), (5.59±1.93), and (16.25±10.27) h , respectively after oral administration of MEQ. The mean areas under the plasma concentration-time curve (AUC0- ) of MEQ, M1, and M2 were (4.88±1.54), (36.93±17.50), and (5.16±1.94) μg h mL-1, respectively after intravenous administration of MEQ; (4.18±0.76), (48.25±20.82), and (4.88±2.21) μg h mL-1 , respectively after intramuscular administration of MEQ; and (1.01±0.40), (48.83±20.71), and (5.54±2.23) μg h mL-1, respectively after oral administration of MEQ. MEQ was rapidly absorbed and metabolized in swine after oral, intramuscular, and intravenous administration. Further studies are required to investigate the double-peak phenomenon observed in the plasma concentration-time profile after oral administration and the pharmacokinetics of other metabolites of MEQ.