Compatible Stability Study And Comparison Of Pharmacokinetics Of Luteolin In Rats On Ixeris Sonchifolia Hance Injection Combined With Ligustrazine Hydrochloride For Injection

Objective:Study the compatible stability of KuDieZi injection（KDZ） and5common injection（0.9%NS,5%GS,10%GS,GNS,SLR） in vitro. Study the compatiblestability of KDZ and Ligustrazine Hydrochloride for injection in vitro.To explorecomparison of pharmacokinetics of luteolin in rats on KDZ combined withLigustrazine Hydrochloride.Increasing the accuracy to resolve adverse effects ofChinese medicine injections and ensuring the clinical safety of drugs.Method:The samples of complexes with KDZ were collected at room temperature（25℃） and refrigerated temperature （4℃） to study the changes of appearance, pHvalue, UV absorbance and insoluble particles number and to determinate the contentof luteolin by using HPLC method.The data obtained were fitted with DAS2.1.2program.By comparing single agent and combined pharmacokinetic parameters afterthe shows,the mean serum concentration of luteolin after iv KDZ or mixed drugs inrats were fitted to a tow-compartment model with a weight of1/C2.Result:1. The appearance, pH, UV absorbance of finished infusion:There is nosignificant change of the appearance, pH, UV absorbance after KDZ combined with0.9%NS,5%GS,10%GS,GNS and SLR at room temperature for24h and inrefrigerated temperature for48h.2. The insoluble particles number of finished infusion:The insoluble particles numberwas in line with the Chinese Pharmacopoeia （2010） when KDZ combined with0.9%NS,5%GS at room temperature for24h and refrigerated temperature for48h.Theinsoluble particles number was outside the specified range after KDZ combined with10%GS, GNS and SLR at room temperature and refrigerated temperature for1h.3. The luteolin content of finished infusion: Luteolin content decreased to less than10%after KDZ combined with0.9%NS,5%GS and SLR at room temperature for24h and refrigerated temperature for48h. Luteolin content decreased more than10%after KDZ combined with10%GS, GNS at room temperature and refrigeratedtemperature for1h. 4. Changes in the mixed solution: After KDZ combined with LigustrazineHydrochloride,no significant changes in appearance and the absorbance of the mixedsolution,pH is reduced by1.92, luteolin content reduced by34%,the insolubleparticles number was outside the specified range at room temperature for1h andrefrigerated temperature for2h.5. Pharmacokinetic impact: The luteolin plasma concentration-time curves of thesingle group and the combination group meet the two-compartment model.The mainpharmacokinetic parameters of the single group: α=0.125±0.0605min^-1，β=0.0162±0.00519min^-1，t_1/2α=6.682±3.0240min, t1/2β=46.927±15.473min，Vc=0.0358±0.0111L/kg， CL=0.00183±0.000408L/min/kg, AUC（0-t）=114.669±12.316（μg/mL） min, AUC（0-∞）=150.230±15.182（μg/mL） min，K₁₂=0.0628±0.0367min^-1，K₂₁=0.0285±0.0143min^-1. The main pharmacokineticparameters of the combination group: α=0.103±0.0468min^-1， β=0.0152±0.00467min^-1，t_1/2α=7.595±2.333min, t1/2β=48.963±14.139min，Vc=0.0352±0.00674L/kg， CL=0.00150±0.000548L/min/kg, AUC（0-t）=129.956±7.955（μg/mL） min, AUC（0-∞）=167.011±9.277（μg/mL） min，K₁₂=0.0483±0.0284min^-1，K₂₁=0.0260±0.0140min^-1.Conclusion: It is stable after KDZ combined with0.9%NS and5%GS at roomtemperature within24h and refrigerated temperature within48h.KDZ should not bediluted by10%GS, GNS or SLR.KDZ should not be combined with LigustrazineHydrochloride for Injection. There was no significant change in pharmacokineticparameters after i.v. administration of KDZ combined with LigustrazineHydrochloride for Injection.