两种米尔贝肟吡喹酮片内服给药在猫的药动学比较研究

发布时间：2019-06-19 20:29

【摘要】：米尔贝肟作为治疗犬恶丝虫及犬猫肠道寄生虫的特效药,具有广谱的杀虫活性、吸收良好、安全性高等特点,临床上广泛用于防治犬猫体内外寄生虫。其与吡喹酮联用,对猫的弓首蛔虫感染具有十分有效的治疗作用。本研究旨在通过对米尔贝肟吡喹酮片在猫体内的药动学研究,来获得相关的药代动力学参数,以评价米尔贝肟在猫体内的药动学特征。这不仅为指导新药设计和临床给药方案的制定提供依据,而且对指导临床合理用药也具有重要的意义。16只成年健康猫随机分成2组,每组8只(公母各半),采用单剂量平行随机对照试验设计,分别进行单剂量(4 mg/kg b.w.,以米尔贝肟计)内服国产米尔贝肟吡喹酮片和进口米尔贝肟吡喹酮片对照品的药动学比较研究。给药后按预定时间点采集血样,采用HPLC法进行血浆中米尔贝肟和吡喹酮含量的测定,实测血药浓度-时间数据采用Winnonlin5.2药动学分析软件计算药代动力学参数。单剂量(4 mg/kg b.w.,以米尔贝肟计)内服米尔贝肟吡喹酮片对照品后,米尔贝肟的平均消除半衰期(T1/2β)约为20.08 h,达峰时间(Tmax)和峰值浓度(Cmax)分别为6.00 h和764.43 ng/mL,平均曲线下面积(AUC)为15.00 ng/L/h,平均滞留时间(MRT)为18.60h；吡喹酮的平均消除半衰期(T1/2β)约为6.27 h,达峰时间(Tmax)和峰值浓度(Cmax)分别为3.88 h和1018.25 ng/mL,平均曲线下面积(AUC)为8.69 ng/L/h,平均滞留时间(MRT)为6.56 h。结果显示猫内服米尔贝肟吡喹酮片对照品后其米尔贝肟在猫体内吸收和消除较吡喹酮稍缓慢。单剂量(4 mg/kg b.w.,以米尔贝肟计)内服米尔贝肟吡喹酮片受试品后,米尔贝肟的平均消除半衰期(T1/2β)约为15.07 h,达峰时间(Tmax)和峰值浓度(Cmax)分别为5.25 h和806.65 ng/mL,平均曲线下面积(AUC)为15.18 ng/L/h,平均滞留时间(MRT)为17.47h,相对生物利用度为101.20%。吡喹酮的平均消除半衰期(T1/2β)约为11.11 h,达峰时间(Tmax)和峰值浓度(Cmax)分别为5.25 h和880.47 ng/mL,平均曲线下面积(AUC)为9.64 ng/L/h,平均滞留时间(MRT)为10.52 h,相对生物利用度为119.16%。与对照品相比,受试品的药动学参数中除米尔贝肟的消除半衰期显著缩短、吡喹酮除达峰时间显著延迟外(0.01P0.05),其他药动学参数统计学差异均不显著(P0.05)。结果表明米尔贝肟受试品与对照品在猫内服给药主要药动学特征相似,这从另一方面亦证实两者具有相似的临床疗效。
[Abstract]:Milbexime, as a special drug for the treatment of canine filariasis and intestinal parasites in dogs and cats, has the characteristics of broad-spectrum insecticidal activity, good absorption and high safety, and is widely used in the prevention and control of parasites in vivo and in vitro. The combination of praziquantel and praziquantel has a very effective therapeutic effect on Toxoplasma gondii infection in cats. The purpose of this study was to obtain the relevant pharmacokinetic parameters by studying the pharmacokinetics of Milbedoxime praziquantel tablets in cats in order to evaluate the pharmacokinetics characteristics of Milbexime praziquantel tablets in cats. This not only provides the basis for guiding the design of new drugs and the formulation of clinical administration plan, but also has important significance for guiding the rational use of drugs in clinic. Sixteen healthy adult cats were randomly divided into two groups with 8 cats in each group (half male and half female). A single dose (4 mg/kg B. W.) was designed by single dose parallel random controlled trial. Comparative study on pharmacokinetics of domestic Milbedoxime praziquantel tablets and imported Milbedoxime praziquantel tablets. The blood samples were collected according to the predetermined time point after administration, and the contents of Milbexime and praziquantel in plasma were determined by HPLC method. The pharmacokinetics parameters were calculated by Winnonlin5.2 pharmacokinetics analysis software. The average elimination half-life (T _ 1 鈮，

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