吡喹酮不同途径给药在大鼠体内药代动力学及自胆汁中的排泄

THE PHARMACOKINETICS AND BILIARY EXCRETION OF PRAZIQUANTEL IN RATS BY DIFFERENT ROUTE OF ADMINISTRATION

大鼠iv吡喹酮20mg/kg,血药浓度时间曲线符合二室开放模型。消除快,t1/2β=0.36±(SD)0.07h。im10,20,40mg/kg或ig100mg/kg后,血药浓度达峰时间较快,但消除相与iv比却相对明显缓慢。MAT_(im)和MAT_(ig)均大于MRT_(ivo)ig的生物利用度为13.2%,有明显首过效应。im则吸收完全,当im10和20mg/kg时消除动力学呈线性关系,而当增至40gg/kg时,有呈非线性趋势。大鼠在im20mg/kg,iv20mg/kg以及ig300mg/kg后,胆汁中均能检测出原形吡喹酮,其浓度以iv最高,im居中,ig最低。

Praziquantel ( PQT ) concentrations in plasma after iv 20 mg/kg decayed rapidly with tip of 0.36 h. The absorption of PQT was rapid following the intramuscular doses of 10,20,40mg/kg or intragastic dose of 100mg/kg, but the phase of elimination was much longer than that after iv. Both of MAT1m and MATig were greater than MRTiv. The bioavailability of ig was 13.2%, suggesting a strong first-pass effect. The kinetics of PQT elimination was linear after intramuscular dose of either 10 or 20 mg/kg, but nonlinear process was found when the dose was increased to 40mg/kg. By any route of iv, im and ig administration, the concentrations of PQT in the bile were much lower than the peripheral plasma concentrations and changed in parallel to the later with high levels after iv, medium levels after im and much low levels after ig.