| Objective:To investigate the rabbit's blood drug level and pharmacokinetic(PK) parameters of 10-hydroxycamptothecin(HCPT)nanoparticle IV bolus injection and to detect the tissue distribution of HCPT nanoparticle in mice via IV injection compared with the results of HCPT injection,evaluation of the pharmacokinetic characteristics of HCPT nanoparticle.Methods:HCPT in rabbit plasma and mice plasma and tissues was determined by reversed-phase HPLC and UV detector. EXCEL software was used in drawing the plasma concentration-time curves,and 3P97 software was used in calculation of compartment model and PK parameters of two HCPT preparations for rabbit.HCPT nanoparticle injection was administered to BALB/C mice by bolus injection at dose of 10 mg·kg-1body weight.At the distribution and elimination time period(post injection time of 15,60,120 min)mice were killed separately.Live,lung,heart,spleen,kidney,stomach,intestine,brain, muscle,fat,testis and blood were colleted.Drug levels in plasma and various tissues were detected.The characteristics of blood concentrations and tissue distribution were contrasted between two preparations at different times by SPSS for Windows 13.0.Results:①The concentration-time profile for HCPT nanoparticle injection could be best described by three-compartment model fitted by 1/C2 weight and the common injection was described by two-compartment model fitted by 1/C2 weight;②Plasma peak concentration of HCPT common injection was three times as many as that of nanoparticle injection in equal dosage.Area under curve(AUC)of HCPT common injection was two-fold higher than that of nanoparticle injection.③Apparent volume of distribution of central compartment(Vc)of HCPT nanoparticle injection was greater than that of nanoparticle injection in equal dosage.④HCPT nanoparticle injection had a longer elimination half life(T1/2β)than that of common injection.⑤The highest concentration of HCPT nanoparticle injection was obtained in liver,the lowest in heart.The concentrations of brain,fat,testis and other tissues were below the detection limit.The sequence of HCPT levels in various tissues was: liver＞kidney＞spleen＞stomach＞lung＞heart;The concentration of drug in intestine was lower than 10μg·g-1.⑥Concentration of nanoparticle injection were higher than common injection in several kinds of tissues(e.g.liver,kidney,spleen,lung, heart)(P＞0.05).⑦HCPT nanoparticle injection was obviously accumulated in liver. The tissue drug concentrations of common injection were lower and there was no apparently accumulated target tissue or organ.Conclusion:Compared with HCPT common injection,HCPT nanoparticle injection can be distributed into organs more extensively.It presents great liver targeting capability and it keeps higher concentration in liver for a longer period.
|
PDF Full Text Request