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Pharmacokinetics and Tissue Distribution Comparison between HCPT Nanoparticle Injection and Common Injection

Author: ZhaoGuoChen
Tutor: LiuYanXia；GaoWeiZhen；KangYi；JiaoJianJie
School: Tianjin Medical University
Course: Pharmacology
Keywords: Anticancer drugs Hydroxycamptothecin Nano Pharmacokinetic Tissue distribution
CLC: R96
Type: Master's thesis
Year: 2008
Downloads: 313
Quote: 1
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Abstract


Objective: To examine injectable nano HCPT intravenous bolus after administration of rabbit plasma concentration over time trends and drug metabolism kinetic parameters measured after the intravenous injection of nano-HCPT injection drug distribution in the various tissues of the mouse. And injection HCPT compare, evaluate the injection of nano HCPT pharmacokinetic properties changes. Methods: HPLC detection of rabbit plasma and mouse tissues and plasma HCPT content; curve using Excel draw drug, using the 3P97 pharmacokinetic calculation software simulation compartment model and calculation HCPT two formulations rabbits drug metabolism power The pharmacokinetic parameters. Select the distribution phase and the elimination phase time point (after administration of 15 min, 60 min and 120 min) mice were sacrificed, liver, lung, heart, spleen, kidney, stomach, intestine, brain, muscle, fat, testis and blood and other 12 kinds of organizations, the determination of the tissue and blood concentration of the drug. SPSS for Windows 13.0 statistical analysis software group comparative analysis between the two formulations. Results: ① injection of rabbit ear vein with HCPT single bolus injection to meet the 1 / C 2 weight two-compartment model, injected with nano HCPT complies 1 / C 2 weight of the three-compartment model. ② injection with HCPT plasma C max 3 times the injection of the same dose using nano HCPT, AUC is the injection of HCPT with nano 2-3 times. ③ same dose injection with the nano HCPT group V c are greater than the injection HCPT group. The ④ injection nano HCPT elimination half-life (T 1/2β ) injection compared with HCPT extend. ⑤ injected with nano HCPT highest concentrations in the liver, lower levels in the heart, muscles close to the detection limit of the amount of drugs, and the content is below the detection limit of the drug in the brain, fat, and testis, the main organs of drug distribution order: liver> kidney> spleen> intestine> stomach> lung> heart; injection HCPT distribution in major organs, lower drug distribution measured in most intestinal average drug concentration below 10μg · g -1 . ⑥ injected with nano HCPT group in the major distribution of organs (liver, kidney, spleen, lung, heart) tissue drug concentrations significantly higher than the injection HCPT group (P <0.05). ⑦ injected with nano-HCPT after administration of the drug in the liver tissue can be a long time to maintain a high concentration, and injected with HCPT group after the administration of the organization the drug concentration is low, there is no significant accumulation in the target tissue or organ. Conclusion: Injection nano HCPT and injection HCPT as compared to more into the tissue and organs, and simultaneously injected with nano HCPT liver tissue the obvious targeting can be a long time in the liver tissue to maintain higher drug concentration .

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