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帕托珠利混悬液在仔猪体内的药动学及生物利用度研究
张小龙,卜仕金,沈佳晨,聂贞,王美红,蒋玥
0
(扬州大学兽医学院)
摘要:
为研究帕托珠利混悬液在仔猪体内的药动学特征及生物利用度,采用平行实验设计方法,将16头 40 日龄健康仔猪随机分成两组,每组8头(公母各半),分别进行单剂量静脉注射(6mg/kg bw)和单剂量口服给药(15mg/kg bw),所有猪给药前禁食12h,给药2h后恢复正常饮食。给药后按预定的采血点采集血样,血浆中帕托珠利的含量采用经验证的 HPLC检测方法进行测定。实测血药浓度数据采用Graphad prism 8.0拟合药时曲线图,并用 Winnonlin5.2计算药动学参数。结果显示,单剂量静脉注射帕托珠利注射液后帕托珠利在仔猪体内主要药动学参数如下:平均消除半衰期(T1/2?)为136.98h,平均滞留时间(MRT)为165.92h,平均药时曲线下面积(AUC0-t)为1570.97 h?μg/mL,平均表观分布容积(Vz)为695.59 mL/kg,平均血浆清除率(CL)为3.77 mL/h?kg;单剂量口服帕托珠利混悬液后帕托珠利在仔猪体内主要药动学参数如下:平均消除半衰期(T1/2?)为134.05h,平均达峰时间(Tmax)为42.00h,平均峰浓度(Cmax)为14.03μg/mL,平均滞留时间(MRT)为173.19h,平均药时曲线下面积(AUC0-t)为2831.00 h?μg/mL,帕托珠利混悬液口服给药绝对生物利用度为72.08%。结果表明,帕托珠利在猪体内分布较差,消除缓慢;仔猪口服帕托珠利混悬液达峰时间较长,但吸收良好。
关键词:  帕托珠利混悬液  仔猪  药动学  生物利用度
DOI:
投稿时间:2020-06-27修订日期:2020-08-22
基金项目:江苏高校优势学科建设工程资助项目( PAPD)
Study on pharmacokinetics and bioavailability of ponazuril suspension in piglets
(College of Veterinary Medicine of Yangzhou Univesity)
Abstract:
To study the pharmacokinetics and bioavailability of ponazuril suspension in piglets, a parallel experimental design method was used. Sixteen healthy 40-day-old piglets were randomly divided into two groups, each with eight heads (half male and half female), given a single dose of intravenous injection (6mg/kg bw) and a single dose of oral administration (15mg/kg bw). All piglets were fasted for 12 hours before administration, and returned to normal diet after 2 hours of administration. Blood samples were collected at predetermined blood collection points after administration and were determined a validated HPLC detection method. The measured data used Graphad prism 8.0 to fit the drug time curve, and Winnonlin 5.2 was used to calculate the pharmacokinetic parameters. The main pharmacokinetic parameters of ponazuril in piglets after single-dose intravenous injection of ponazuril injection are as follows: the average elimination half-life (T1/2β) was 136.98h, the average residence time (MRT) was 165.92h, the area under the average drug time curve(AUC0-t)was 1577.97 h.μg/mL, the mean apparent volume of distribution (Vz) was 695.59 mL/kg and the mean plasma clearance (CL) was 3.77 mL/h·kg. The main pharmacokinetic parameters of ponazuril in piglets after single-dose oral ponazuril suspension are as follows: the average elimination half-life (T1/2β) was 134.05h, the average peak time (Tmax) was 42.00h, the average peak concentration (Cmax) was 14.03μg/mL, the average retention time (MRT) was 173.19 h and the area under the average drug time curve (AUC0-t)was 2831.00 h·μg/mL, the absolute bioavailability of ponazuril suspension was 72.08%. The results showed that the distribution of ponazuril in pigs was poor and its elimination was slow. The ponazuril suspension was taken for a long time for oral administration,but it was well absorbed.
Key words:  ponazuril suspension  piglet  pharmacokinetics  bioavailability

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