Investigation Of Pharmacokinetics For Hydroxycamptothecin-Loaded Microcapsules

10-hydroxycamptothecin (HCPT) is the clinical application of camptothecin drugs, widely used in clinical treatment of various malignancies. However, due to HCPT has a low solubility in water, structure, poor stability, short half-life in vivo defects, limiting its clinical application.HCPT early microcapsules in vitro release test results show that the microcapsules contain medicine system for the short half-life of HCPT and other drugs, is a promising drug delivery vector system.In this study, establish the method for the concentration determination of HCPT in mice plasma tissues and feces, to provide for the delivery of clinical data HCPT.This study established the high performance liquid chromatography HCPT concentration in mouse plasma method, making use of concentration-time curve excel, the use of pharmacokinetic calculation software (Kinetics 5.0) Calculation of pharmacokinetic parameters. HCPT The peak concentration (Cmax) was 17.80 ng·mL-1, peak time (Tmax) was 0.17 h, the half-life (T1/2) to 9.03 h, mean residence time (MRT) was 14.33 h,24 h of drug the area under curve (AUC0-24) was 90.44 h·ng·mL-1,0-∞area under the curve of drug time (AUC0-∞) was 111.50 h·ng·mL-1.4 double-HCPT microcapsules Cmax was 10.73 ng·mL-1, Tmax was 0.67 h, T1/2 was 13.28 h, MRT was 21.63 h,24 h of the AUC0-24 was 60.33 h·ng·mL-1, 0-∞of the AUC0-∞was 97.74 h·ng·mL-1.7 double-HCPT microcapsules Cmax was 13.78 ng·mL-1, Tmax was 0.67 h, T1/2 was 25.39 h, MRT was 39.29 h,24 h of the AUC0-24 was 89.46 h·ng·mL-1, AUC0-∞was 211.89 h·ng·mL-1; 10 bilayers HCPT microcapsules Cmax was 11.50 ng·mL-1, Tmax was 1.5 h, T1/2 was 30.42 h, MRT was 51.23 h, AUC0-24 was 68.79 h·ng·mL-1, AUC0-∞was 219.09 h·ng·mL-1.4 double layer microcapsules HCPT relative bioavailability is 84.62%.7double layer microcapsules HCPT relative bioavailability of 4 double layer microcapsules HCPT relative bioavailability is 190.03%.10 double layer microcapsules HCPT relative bioavailability is196.49%. HCPT microcapsules in various tissues from a high in the end of the distribution of the order:liver, kidney, lung, spleen, brain, heart. This shows that HCPT significantly on liver targeting. There is HCPT microcapsule little distribution in the heart, brain, only 10 in the layer a small amount of the distribution of HCPT microcapsules. Female mice after oral administration in mice feces HCPT content of 9.46%-19.55%, while male mice feces in the content of 9.32%-14.59 HCPT, we can see from the results there are about 10%～20% of the original drug HCPT form of discharge.