土霉素和磺胺甲噁唑在三种淡水鱼体内的药动学和残留研究

【作者】 李雪梅；

【导师】 张其中；

【作者基本信息】 西南师范大学 ， 水生生物学， 2005， 硕士

【摘要】 水产病害防治是水产养殖中不可缺少的主要环节,长期以来,药物防治在生产实践中占主导地位。我国水产药物使用前未在水产动物中作药物代谢和残留消除规律研究,水产上普遍存在盲目用药现象。这样生产出的水产品普遍存在抗菌药物残留,一方面严重阻碍我国水产品出口创汇,另一方面也影响我国消费者的健康。因此,目前我国急需研究药物在水产养殖动物中的动力学和残留消除规律,从根本上消除水产品中的药物残留。本文主要报道了土霉素和磺胺甲噁唑在三种淡水鱼体内的药动学和残留研究结果: 在（21±1）℃水温条件下,给草鱼单剂量100mg/kg口灌土霉素,血液中药物动力学数据符合两室模型:吸收半衰期(t_{（1/2）（ka）})、分布半衰期(t_{（1/2）（a）})和消除半衰期(t_{（1/2）（B）})分别为1.57h、6.52h和86.85h。通过研究土霉素在草鱼体内的药物动力学及残留发现,草鱼对土霉素的吸收、消除都很缓慢;最后一次给药后的25d及以后,肌肉中检测不出药物,休药期至少需要25d以上。 在（10±1）℃水温条件下,给鲫鱼单剂量50mg/kg口灌和肌肉注射土霉素,结果表明:肌肉注射时,鲫鱼对土霉素的吸收比口灌时快;两种给药方式下,肝脏中都存在着再吸收;同一给药方式下,肾脏和肝脏中的最高药物浓度比肌肉和血液中的高。 在（21±）℃水温条件下,给草鱼单剂量150mg/kg口灌磺胺甲噁唑时,磺胺甲噁唑在血清中的吸收半衰期(t_1/2（ka）))、分布半衰期(t_{（1/2）（a）})和消除半衰期（t（（1/2）（B）））分别为2.03h、2.44h和36.40h。通过多剂量（150mg/kg/d,连给10d）口灌和混饲给草鱼磺胺甲噁唑,研究该药在草鱼体内的残留发觋:给药后的初期,肌肉中磺胺甲噁唑的浓度高于肝脏和肾脏中的浓度;口灌给药后的第19d,肌肉中的药物含量为（0.10±0.15）mg/kg,第24d及以后药物浓度低于检测限;而混饲给药的第24d,肌肉中药物含量为（0.09±0.02mg/kg）,第27d及以后,药物浓度低于检测限。通过多剂量（30mg/kg/d,连给10d）口灌和混饲给草鱼磺胺甲噁唑的增效剂甲氧苄啶,研究该药在草鱼体内的残留发现:消除期间,组织中甲氧苄啶的含量高于血液中的含量。口灌给药后的第24d,甲氧苄啶浓度低于检测限,混饲给药后,第19d后肌肉中药物浓度低于检测限,由于个体差异,第24d肌肉中药物浓度为0.18mg/kg,第27d及以后,肌肉中甲氧苄啶浓度低于检测限。所以,休更多还原

【Abstract】 It’s indispensable to prevent and treat aquatic diseases. And drug prevention has taken a leading position for a long time in aquaculture. It’s very general to abuse drugs for pharmacokinetics and residues of drugs in aquatic product are not studied, which results in antibiotic residues. Drug residues not only influence our country’s export earning of aquatic product, but also do harm to consumers. So it’s urgent for us to do some researches on pharmacokinetics and residues of drugs, in order to avoid residues in aquatic products. The present study deals with pharmacokinetics and residues of oxytetracycline （OTC） and sulfamethoxazole （SMZ） in three freshwater fishes, the results are as. follows:Grass carp were treated orally via stomach tube at a single dosage of 100 mgOTC/kg at water temperature （21±1） °C. The data of pharmacokinetics were conformed to a two-compartment model. The absorption half-life （t₁/2 （ka）） was 1.57 h and the distribution half-life（t1/2（a）） was 6.52 h and the elimination half-life（t1/2（B）） was 86.85 h in serum. The present study dealt with the pharmacokinetic profile and residue elimination of OTC in grass carp. The results showed that absorption and elimination of OTC were slow, suggesting a need for long withdrawal periods （at least 25 days） prior to use of dosed fish for human consumption following oral administrations with feed at a dose of 100 mg/kg/day for 7 days at water temperature （21±1） ℃.Comparative pharmacokinetics in serum and distribution in tissues were studied in Carassius auratus administrated following two administration routes at water temperature（10±1）℃. The results indicated that OTC can be absorbed faster in serum of Carassius auratus administrated by intramuscular injection than orally via stomach tube. OTC concentrations were highest in kidney and lowest in muscle and redistribution existed in liver of Carassius auratus administrated following two administration routes.Grass carp were treated orally at a single dosage of 150 mgSMZ/kg at water temperature（21 ±1）℃. The absorption half-life (t1/2（ka） was 2.03 h and the distribution half-life（t1/2 （a） ） was 2.44 h and the elimination half-life（t1/2 （B） ） was 36.40 h in serum.The present study dealt with residue elimination of SMZ in grass carp administrated orally at a dosage of 150 mg SMZ and 30 mg TMP/kg/d for 10 days via stomach tube and with feed. And the results showed that SMZ concentrations in muscle were higher than those in kidney and liver during SMZ-elimination periods. SMZ concentrations were （0.10±0.15）mg/kg on the 19th day and fell bellow the detection limit （0.05 g/ml） on the 24th day in muscle of grass carp administrated orally via stomach tube. SMZ residues were （0.09±0.02 ） mg/kg on the 24th day and fell below the detection limit on the 27th day in the muscle of grass carp orally with SMZ-medicated feed. The residue elimination in grass carp showed that TMP concentrations in serum were lower than tissues during TMP-elimination periods. TMP concentrations fell below detection limit on the 24th day in muscle of grass carp administrated orally via stomach tube. TMP concentrations were 0.18 mg/kg on the 24th and fell below detection limit on the 27th day in muscle of grass carp administrated orally with feed. We suggested a withdrawal periods （at least 27 days） prior to use of dosed fish for human consumption following oral administrations at a dose of 150 mgSMZ and 30 mgTMP/kg/d for 10 days at water temperature （ 21 ±1） .Pengze crucian carp were treated orally at a single dosage of 150 mgSMZ /kg at water temperature （18±2.5 ） . The absorption half-life （U/2 （ka）） was 2.54 h and the distribution half-life(t1/2（a） was 3.86 h and the elimination half-life（t1/2tB>） of SMZ was 38.94 h in serum. The present study dealt with residue elimination of SMZ in pengze crucian carp administrated orally at a dosage of 150 mgSMZ and 30 mgTMP/kg/d for 10 days via stomach tube and with feed. And the results showed that SMZ concentrations in muscle were higher than those in kidney and liver during SMZ-elimination periods. The residue elimination in Pengze crucian carp showed that SMZ concentrations in muscle were higher than those in kidney and liver during SMZ-elimination periods. SMZ concentrations were highest in serum and tissues of pengze crucian carp administrated both orally via stomach tube and with feed on the 1st day. SMZ residues fell below 0.1 g/ml on the 21th and fell bellow the 0.05 jug/ml on the 22th and 24th day in muscle of pengze crucian carp administrated orally via更多还原