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目的研究海洋新骨架小分子南强菌素经单次静脉注射后在Wistar大鼠体内的药动学、组织分布及排泄特征。方法 48只Wistar大鼠(雌雄各半)分为8组(每组雌雄各三只),3组分别尾静脉注射南强菌素10、20、30 mg·kg-1,液相色谱-串联质谱法(LC-MS/MS)测定其血药浓度,DAS2.0计算药动学参数;其余5组单次尾静脉给予南强菌素20 mg·kg-1,其中3组大鼠给药后0.5、2、3 h麻醉处死、解剖测定南强菌素组织分布,1组给药后收集0~2 h、>2~4 h、>4~8 h、>8~24 h的尿液粪便评价南强菌素的排泄过程,1组麻醉后插管收取0~2 h、>2~16 h、>16~24 h胆汁评价胆汁排泄。结果大鼠分别静脉单次注射10、20、30 mg·kg-1南强菌素后,t蚝虔z分别为(2.09±0.68)、(2.44±0.35)、(2.57±1.33)h,AUC0-8 h分别为(3 378±544)、(3 492±460)、(4 451±573)μg·h·L-1;单次静脉给药20 mg·kg-1,0.5 h后肾脏组织中的南强菌素含量最高(1 736.8 ng·g-1),肺脏及脾脏次之;给药2 h后,多数组织中已经检测不到或仅能检测到极少量南强菌素;原型药物经尿样和胆汁的排泄率分别为1.87%和0.91%,粪便的排泄率极低,低于总给药量的0.01%。结论单次给予南强菌素,各剂量组的AUC0-8 h、ρmax和t蚝虔z用SPSS进行相关检验,无显著差异(P>0.05),表明在置信度(单双侧)0.05水平上剂量与AUC0-8 h、ρmax和t蚝虔z均不相关;原型药物经粪便和尿样排泄率较低,1~24 h内仅有1.87%从尿液中排出。
OBJECTIVE: To study the pharmacokinetics, tissue distribution and excretion of a new marine small-molecule streptogramin in Wistar rats after a single intravenous injection. Methods 48 Wistar rats were divided into 8 groups (3 male and 3 female). The rats in each group were injected with 10, 20 and 30 mg · kg-1 of ST, Mass spectrometry (LC-MS / MS) was used to determine the plasma concentration. DAS 2.0 was used to calculate the pharmacokinetic parameters. The other 5 groups were given a single intravenous injection of 20 mg · kg -1 of S. aureus. After 0.5, 2, 3 h anesthesia was sacrificed, the distribution of Strychnine was determined by anatomy, and the urine of 0-2 h,> 2-4 h,> 4-8 h and> 8-24 h was collected in group 1 Fecal evaluation of the process of excretion of streptozotocin, a group of anesthetized intubation charge 0 ~ 2 h,> 2 ~ 16 h,> 16 ~ 24 h bile excretion evaluation. Results After a single injection of 10, 20 and 30 mg · kg-1 S. aureus into the venous parenchyma of rats, the values of t-hs-p value were (2.09 ± 0.68), (2.44 ± 0.35), (2.57 ± 1.33) (3 372 ± 544), (3 492 ± 460) and (4 451 ± 573) μg · h · L -1 for 8 h, respectively. After a single intravenous injection of 20 mg · kg-1, (1 736.8 ng · g-1), followed by the lung and spleen; 2 h after administration, no detectable or only very small amounts of HS were detected in most tissues; the prototype Urine samples and bile excretion rates were 1.87% and 0.91%, excretion rate was very low, less than 0.01% of the total dose. CONCLUSIONS: Scutellaria toxoplasmosis is a single dose of AUC0-8 h, ρmax and t-hysterosis in each dose group were tested by SPSS, there was no significant difference (P> 0.05), indicating that in confidence (single and double) 0.05 level The upper dose was not related to AUC0-8 h, ρmax and t oyster z; the excretion rate of the prototype drug was lower after excrement and urine sample, only 1.87% within 1 ~ 24 h was excreted from the urine.