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恩诺沙星在中华草龟体内的药物代谢动力学研究

发布时间:2018-08-11 11:31  文章来源:笔耕文化传播
【摘要】:中华草龟(Chinemys reevesiis)是我国常见的龟类,不仅可以入药、食用,还可作家庭观赏,在我国养殖范围广泛,是除中华鳖外的又一大经济龟鳖物种。随着养殖规模的不断扩大,高密度集约化、温室驯养、滥用抗生素药物、疾病频发等问题越来越严重,但是相应的疾病防治研究却陷入瓶颈,发展缓慢。恩诺沙星(Enrofloxacin),属于人工合成喹诺酮类药物,对于革兰氏阳性菌、阴性菌和霉形体都具有很好的抑制效果,具有广谱抗菌性;不仅毒副作用小、有良好的组织分布性,并且与其他抗生素之间无交叉耐药性,是一种较好的抗菌药物。本实验研究比较了同一给药浓度下,肌注和胃插管术强制口服两种给药方式下,恩诺沙星在中华草龟体内的药物代谢动力学规律。选取20只健康中华草龟,每组10只,随机分为2组,分别为肌注组和胃插管强制口服组,给药量均为10mg.kg-1。给药后,分别在0h,0.5h,4h,8h,12h,24h,48h,96h,120h,144h,172h和196h后于龟颈静脉窦处采血,是国内首次在龟类药动学研究中成功实现在同一个体连续采血。应用液相色谱串联质谱法测定数据,Kinetic4.4软件的非房室模型分析药时数据。胃插管强制口服给药主要药动学参数为Cmax7.49μg/ml、Tmax12h、T1/2λz为99.85h、AUC0-∞为531.67 h*μg/m L;肌注给药主要药动学参数为Cmax5.85μg/ml、Tmax4h、T1/2λz为30.42h、AUC0-∞为193.6 h*μg/mL。两种不同给药条件下,肌注恩诺沙星比胃插管强制口服更快达到最高血药浓度,表明肌注恩诺沙星在中华草龟体内吸收更快;胃插管强制口服给药的Cmax和AUC均高于比肌注给药,表明胃插管强制口服恩诺沙星在中华草龟体内吸收更完全,分布更广泛效果更好。恩诺沙星在中华草龟体内消除缓慢,MRT长,胃插管强制口服给药MRT显著长于肌注给药,其血药浓度保留时间长,效果更持久。不同给药剂量下,肌注恩诺沙星在中华草龟体内的药物代谢动力学特征也存在差异。选取健康中华草龟20只,随机均分为2组,分别肌注给药10mg.kg和20mg/kg。应用液相色谱串联质谱法测定数据,Kinetic4.4软件的非房室模型分析药时数据。10mg/kg剂量,主要药动学参数为:Cmax为5.85μg/ml、Tmax为4h、T1/2λz为30.42h、AUC0-∞为193.6 h*μg/m L;20mg/kg剂量,主要药动学参数为:Cmax为11.3μg/ml、Tmax为8h、T1/2λz为47.04h、AUC0-∞为597.46 h*μg/mL。两种给药剂量下,高剂量组达峰时间是低剂量组的2倍,Cmax和AUC显著高于低剂量组,且196h时高浓度组血药浓度为0.31μg/mL,是低剂量组((0.06±0.03)μg/mL)的5倍,差异显著。可见,不同剂量恩诺沙星在中华草龟体内药动学特征有一定差异,20mg/kg组吸收更全面,相对生物利用度高,但是所需的吸收时间和代谢时间均较长。同时,本文在肌注相同剂量条件下,针对恩诺沙星在中华草龟体内的代谢产物是否为环丙沙星,以及其代谢规律进行了探究。研究结果表明,恩诺沙星在中华草龟体内可代谢转化为环丙沙星,但其代谢率远远低于畜禽类,体内抗菌作用主要依赖原药恩诺沙星。综上,不同给药剂量和给药方式对恩诺沙星在中华草龟体内的药物代谢均存在影响。当需较快达到疗效时,建议肌注恩诺沙星,需持续给药且龟体代谢状态正常时,建议胃插管强制口服恩诺沙星。10mg/kg和20mg/kg给药剂量在中华草龟体内均分布广泛,吸收良好,但考虑药物残留问题,建议选择10mg/kg为给药剂量,并隔天给药。
[Abstract]:Chinese turtle (Chinemys reevesiis) is a common turtle in China. It can not only be used as medicine, edible, but also be enjoyed by the family. It is a large economic turtle species besides Chinese turtle. With the continuous expansion of culture scale, high density and intensive cultivation, greenhouse domestication, abuse of antibiotics, and the frequent occurrence of diseases have become more and more serious. Enrofloxacin, a synthetic quinolone drug, has a good inhibitory effect on Gram-positive bacteria, negative bacteria and mycoplasma, and has a broad spectrum of antimicrobial activity; it not only has a small toxic side effects, but also has a good tissue distribution. The pharmacokinetics of enrofloxacin in Chinese turtles was compared between intramuscular injection and gastric intubation at the same concentration. Twenty healthy Chinese turtles were randomly divided into two groups. After administration, blood samples were collected at the jugular sinus of tortoises at 0 h, 0.5 h, 4 h, 8 h, 12 h, 24 h, 48 h, 96 h, 120 h, 144 h, 172 h and 196 h respectively. It was the first time in China that the same individual was successfully collected in the study of tortoise pharmacokinetics. The main pharmacokinetic parameters were Cmax 7.49 ug/ml, Tmax 12 h, T1/2 lambda Z 99.85 h, AUC 0-infinity 531.67 h * ug/ml, intramuscular injection Cmax 5.85 ug/ml, Tmax 4 h, T1/2 lambda Z 30.42 h, AUC 0-infinity 193.6 ug/mL. The results showed that enrofloxacin was absorbed more quickly by intramuscular injection than by gastric intubation, and the concentration of CMAx and AUC were higher by intramuscular administration than by gastric intubation. Enrofloxacin was slowly eliminated in Chinese turtles and had longer MRT. The drug concentration in blood was longer than that of intramuscular injection. The pharmacokinetic characteristics of enrofloxacin in Chinese turtles were also different at different doses. 20 healthy Chinese turtles were selected and randomly assigned to receive intramuscular injection. The pharmacokinetic parameters were as follows: Cmax 5.85 ug/ml, Tmax 4 h, T1/2 lambda Z 30.42 h, AUC 0-uuuuuuuuuuuuuuuuuuuuuuuuuuuuuuu Cmax was 11.3 ug/ml, Tmax was 8 hours, T1/2 lambda Z was 47.04 hours, AUC 0- The pharmacokinetic characteristics of enrofloxacin in Chinese turtle were different. The 20mg/kg group had more comprehensive absorption and higher relative bioavailability, but the absorption time and metabolic time were longer. At the same time, the metabolites of enrofloxacin in Chinese turtle were ciprofloxacin and its substitutes under the same dosage of intramuscular injection. The results showed that enrofloxacin could be metabolized into ciprofloxacin in Chinese turtles, but its metabolic rate was much lower than that of livestock and poultry. The antimicrobial activity of enrofloxacin in vivo was mainly dependent on enrofloxacin. It is suggested that the dosage of enrofloxacin administered by gastric intubation forcing oral administration of enrofloxacin at doses of 10 mg/kg and 20 mg/kg is widely distributed and well absorbed in Chinese turtles, but considering the drug residue, it is suggested to choose 10 mg/kg as the dosage and give it every other day. Medicine.
【学位授予单位】:上海海洋大学
【学位级别】:硕士
【学位授予年份】:2017
【分类号】:S948

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