發(fā)布時(shí)間：2019-06-19 20:29

【摘要】：米爾貝肟作為治療犬惡絲蟲(chóng)及犬貓腸道寄生蟲(chóng)的特效藥,具有廣譜的殺蟲(chóng)活性、吸收良好、安全性高等特點(diǎn),臨床上廣泛用于防治犬貓?bào)w內(nèi)外寄生蟲(chóng)。其與吡喹酮聯(lián)用,對(duì)貓的弓首蛔蟲(chóng)感染具有十分有效的治療作用。本研究旨在通過(guò)對(duì)米爾貝肟吡喹酮片在貓?bào)w內(nèi)的藥動(dòng)學(xué)研究,來(lái)獲得相關(guān)的藥代動(dòng)力學(xué)參數(shù),以評(píng)價(jià)米爾貝肟在貓?bào)w內(nèi)的藥動(dòng)學(xué)特征。這不僅為指導(dǎo)新藥設(shè)計(jì)和臨床給藥方案的制定提供依據(jù),而且對(duì)指導(dǎo)臨床合理用藥也具有重要的意義。16只成年健康貓隨機(jī)分成2組,每組8只(公母各半),采用單劑量平行隨機(jī)對(duì)照試驗(yàn)設(shè)計(jì),分別進(jìn)行單劑量(4 mg/kg b.w.,以米爾貝肟計(jì))內(nèi)服國(guó)產(chǎn)米爾貝肟吡喹酮片和進(jìn)口米爾貝肟吡喹酮片對(duì)照品的藥動(dòng)學(xué)比較研究。給藥后按預(yù)定時(shí)間點(diǎn)采集血樣,采用HPLC法進(jìn)行血漿中米爾貝肟和吡喹酮含量的測(cè)定,實(shí)測(cè)血藥濃度-時(shí)間數(shù)據(jù)采用Winnonlin5.2藥動(dòng)學(xué)分析軟件計(jì)算藥代動(dòng)力學(xué)參數(shù)。單劑量(4 mg/kg b.w.,以米爾貝肟計(jì))內(nèi)服米爾貝肟吡喹酮片對(duì)照品后,米爾貝肟的平均消除半衰期(T1/2β)約為20.08 h,達(dá)峰時(shí)間(Tmax)和峰值濃度(Cmax)分別為6.00 h和764.43 ng/mL,平均曲線(xiàn)下面積(AUC)為15.00 ng/L/h,平均滯留時(shí)間(MRT)為18.60h；吡喹酮的平均消除半衰期(T1/2β)約為6.27 h,達(dá)峰時(shí)間(Tmax)和峰值濃度(Cmax)分別為3.88 h和1018.25 ng/mL,平均曲線(xiàn)下面積(AUC)為8.69 ng/L/h,平均滯留時(shí)間(MRT)為6.56 h。結(jié)果顯示貓內(nèi)服米爾貝肟吡喹酮片對(duì)照品后其米爾貝肟在貓?bào)w內(nèi)吸收和消除較吡喹酮稍緩慢。單劑量(4 mg/kg b.w.,以米爾貝肟計(jì))內(nèi)服米爾貝肟吡喹酮片受試品后,米爾貝肟的平均消除半衰期(T1/2β)約為15.07 h,達(dá)峰時(shí)間(Tmax)和峰值濃度(Cmax)分別為5.25 h和806.65 ng/mL,平均曲線(xiàn)下面積(AUC)為15.18 ng/L/h,平均滯留時(shí)間(MRT)為17.47h,相對(duì)生物利用度為101.20%。吡喹酮的平均消除半衰期(T1/2β)約為11.11 h,達(dá)峰時(shí)間(Tmax)和峰值濃度(Cmax)分別為5.25 h和880.47 ng/mL,平均曲線(xiàn)下面積(AUC)為9.64 ng/L/h,平均滯留時(shí)間(MRT)為10.52 h,相對(duì)生物利用度為119.16%。與對(duì)照品相比,受試品的藥動(dòng)學(xué)參數(shù)中除米爾貝肟的消除半衰期顯著縮短、吡喹酮除達(dá)峰時(shí)間顯著延遲外(0.01P0.05),其他藥動(dòng)學(xué)參數(shù)統(tǒng)計(jì)學(xué)差異均不顯著(P0.05)。結(jié)果表明米爾貝肟受試品與對(duì)照品在貓內(nèi)服給藥主要藥動(dòng)學(xué)特征相似,這從另一方面亦證實(shí)兩者具有相似的臨床療效。
[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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