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| Pharmacokinetics of Cyadox and Its Major Metabolites in Swine After Intravenous and Oral Administration |
| ZHAO Ning, WANG Lin, LU Xiao-xiong, JIA Hui-qin, FANG Bing-hu, ZENG Zhen-ling , DING Huanzhong |
| Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, P.R. China |
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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 (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.
Abstract 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.
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Received: 25 October 2011
Accepted:
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| Fund: This study was supported by the National Basic Research Program of China (2009CB118805) and the Key Technologies R&D Program of China during the 11th-Five Year Plan period (2009BADB7B05-03). |
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Corresponding Authors:
Correspondence DING Huan-zhong, Tel: +86-20-85284896, Mobile: 13751886811, E-mail:hzding@scau.edu.cn
E-mail: hzding@scau.edu.cn
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| About author: ZHAO Ning, Tel: +86-20-85284896, E-mail: zhaoning520527@126.com; |
Cite this article:
ZHAO Ning, WANG Lin, LU Xiao-xiong, JIA Hui-qin, FANG Bing-hu, ZENG Zhen-ling , DING Huanzhong.
2013.
Pharmacokinetics of Cyadox and Its Major Metabolites in Swine After Intravenous and Oral Administration. Journal of Integrative Agriculture, 12(3): 495-501.
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| [1]Benet L Z, Galeazzi R L. 1979. Noncompartmentaldetermination of the steady-state volume ofdistribution. Journal of Pharmaceutical Sciences, 68,1071-1074[2]Cutler D J 1978. Theory of the absorption time, an adjunctto conventional bioavailability studies. Journal ofPharmacy and Pharmacology, 30, 476-478[3]Ding M X, Wang Y L, Zhu H L, Yuan Z H. 2006. Effects ofcyadox and olaquindox on intestinal mucosal immunityand on fecal shedding of Escherichia coli in piglets.Journal of Animal Science, 84, 2367-2373[4]Fang G J, He Q H, Zhou S Q, Wang D J, Zhang Y L, Yuan ZH. 2006. Subchronic oral toxicity study with cyadox inWistar rats. Food and Chemical Toxicology, 44, 36-41[5]Gibaldi M, Perrier D. 1982. Pharmacokinetics. New York,Marrcel Dekker.de Graaf G J, Spierenburg T J. 1988. Liquid chromatographicdetermination of cyadox in medicated feeds and in thecontents of the porcine gastrointestinal tract withfluorescence detection. Journal of Chromatography,447, 244-248[6]He Q H, Fang G J, Wang Y L, Wei Z C, Wang D J, Zhou S Q,Fan S X, Yuan Z H. 2006. Experimental evaluation ofcyadox phototoxicity to Balb/c mouse skin.Photodermatology Photoimmunology andPhotomedicine, 22, 100-104[7]Huang L. 2005. Effectiveness and safety studies of cyadoxin broilers. Ph D thesis, Huazhong AgriculturalUniversity, Wuhan, China. (in Chinese)[8]Huang L L, Wang Y L, Tao Y F, Chen D M, Yuan Z H. 2008.Development of high performance liquidchromatographic methods for the determination ofcyadox and its metabolites in plasma and tissues ofchicken. Journal of Chromatography (B - AnalyticalTechnologies in the Biomedical and Life Sciences), 874, 7-14[9]Liu Z Y, Huang L L, Dai M H, Chen D M, Tao Y F, Wang YL, Yuan Z H. 2009. Metabolism of cyadox in rat, chickenand pig liver microsomes and identification ofmetabolites by accurate mass measurements usingelectrospray ionization hybrid ion trap/time-of-flightmass spectrometry. Rapid Communications in MassSpectrometry, 23, 2026-2034[10]Qiu Y. 2003. Pharmacokinetics residue depletion of cyadoxin swine. Ph D thesis, Huazhong Agricultural University,Wuhan, China. (in Chinese)[11]Sestakova I, Kopanica M. 1988. Determination of cyadoxand its metabolites in plasma by adsorptivevoltammetry. Talanta, 35, 816-818[12]Tokosova M. 1990. The effect of cyadox and virginiamycinon Marek’s disease in chickens. Veterinarni Medicina,35, 105-112[13]de Vries H, Bojarski J, Donker A A, Bakri A, Beyersbergenvan Henegouwen G M. 1990. Photochemical reactionsof quindoxin, olaquindox, carbadox and cyadox withprotein, indicating photoallergic properties. Toxicology,63, 85-95[14]Xu N, Huang L L, Liu Z L. 2011. Metabolism of cyadox bythe intestinal mucosa microsomes and gut flora ofswine, and identification of metabolites by highperformanceliquid chromatography combined with iontrap/time-of-flight mass spectrometry. RapidCommunications in Mass Spectrometry, 25, 2333-2344[15]Yamaoka K, Nakagawa T, Uno T. 1978. Statistical momentsin pharmacokinetics. Journal of Pharmacokinetics andBiopharmaceutics, 6, 547-558[16]Yin J. 2003. Pharmacokinetics residue depletion of cyadoxin carp. MSc thesis, Huazhong Agricultural University,Wuhan, China (in Chinese)[17]Zhang Y L, Huang L L, Chen D M, Fan S X, Wang Y L, TaoY F, Yuan Z H. 2005. Development of HPLC methodsfor the determination of cyadox and its main metabolitesin goat tissues. Analytical Sciences, 21, 1495-1499 |
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