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摘要
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 (AUC(0-infinity)) were (0.38 +/- 0.03) mu g mL(-1) h (CYX), (0.018 +/- 0.002) mu g mL(-1) h (BDCYX) and (0.17 +/- 0.02) mu g mL(-1) h (CYX-1-O), respectively. The terminal elimination half-lives (t(1/2 lambda z)) 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 (C-max) of (1.08 +/- 0.06) mu g mL(-1) (CYX), (0.0068 +/- 0.0004) mu g mL(-1) (BDCYX) and (0.25 +/- 0.03) mu g mL(-1) (CYX-1-O) were observed at T-max 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: AUC(0-infinity) were (0.42 +/- 0.04) mu g mL(-1) h (CYX), (1.38 +/- 0.14) mu g mL(-1) h (BDCYX), (0.59 +/- 0.02) mu g mL(-1) h (CYX-1-O) and (1.48 +/- 0.09) mu g mL(-1) h (QCA), respectively. t(1/2 lambda z) 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, C(max)s of (0.033 +/- 0.002) mu g mL(-1) (CYX), (0.22 +/- 0.03) mu g mL(-1) (BDCYX), (0.089 +/- 0.005) mu g mL(-1) (CYX-1-O), and (0.17 +/- 0.01) mu g mL(-1) (QCA) were observed at T-max 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 (AUC(0-infinity))of metabolites were higher than that of CYX after p.o. administration, and the elimination half-lives (t(1/2 lambda z)) of QCA were longer than those of CYX, CYX-1-O, and BDCYX after oral administration.
- 出版日期2013
- 单位华南农业大学
