摘要
目的研究木犀草素固体分散体的体外溶出度和在Beagle犬体内的药动学行为。方法按照2020年版《中国药典》(四部)“溶出度测定法”第二法(桨法)测定木犀草素固体分散体的溶出度。采用超高效液相色谱-串联质谱(UPLC-MS/MS)法测定Beagle犬血浆中木犀草素浓度。取Beagle犬12只,随机分为木犀草素原料药组和木犀草素固体分散体组,每组6只,均口服相应药物,给药剂量相当于木犀草素10 mg/kg。分别于给药前(0 h)、给药后5、10、15、30、45 min和1、2、4、6、8、10、12、24、48 h取血,用乙腈沉淀蛋白后,采用UPLC-MS/MS法测定Beagle犬体内木犀草素血药浓度。运用DAS 3.2.8药动学软件,采用非房室模型计算药动学参数。结果木犀草素固体分散体在纯水、0.1%十二烷基硫酸钠溶液中的溶出度高于木犀草素原料药,在0.1%十二烷基硫酸钠溶液中120 min的溶出度可达95%。木犀草素固体分散体组Beagle犬体内木犀草素的峰浓度(cmax)是木犀草素原料药组的5.62倍,其相对生物利用度为348%。与木犀草素原料药组比较,木犀草素固体分散体组Beagle体内木犀草素的cmax和药时曲线下面积均显著升高,表观分布容积显著降低(P<0.05)。结论木犀草素固体分散体可提高木犀草素的体外溶出度和在Beagle犬体内的生物利用度。
OBJECTIVE To explore in vitro dissolution and in vivo pharmacokinetics of Luteolin solid dispersion in Beagle dogs.METHODS The dissolution of Luteolin solid dispersion was investigated according to the second method(paddle method)of the“dissolution determination method”in the 2020 edition of Chinese Pharmacopoeia(PartⅣ).UPLC-MS/MS method was established to determine the concentration of luteolin in the plasma of Beagle dogs.Twelve Beagle dogs were randomly divided into luteolin group and Luteolin solid dispersion group,with 6 dogs in each group.They were given relevant medicine orally at the dose of 10 mg/kg luteolin.Blood was collected before medication(0 h),at 5,10,15,30,45 min and 1,2,4,6,8,10,12,24,48 h after administration.After protein precipitation with acetonitrile,the blood concentration of luteolin in Beagle dogs was determined by UPLC-MS/MS and the major pharmacokinetic parameters were calculated with non-compartmental models by using DAS 3.2.8 pharmacokinetic software.RESULTS The dissolutions of Luteolin solid dispersion in purified water and 0.1%sodium dodecyl sulfate solution was significantly higher than those of luteolin;the dissolution rate reached 95%in 0.1%sodium dodecyl sulfate solution for 120 minutes.The peak concentration(cmax)of luteolin in the Luteolin solid dispersion group of Beagle dogs was 5.62 times higher than the luteolin group,and the relative bioavailability was 348%.Compared with luteolin group,cmax and the area under the drug time curve of luteolin in the Luteolin solid dispersion group of Beagle dogs were significantly increased,while the apparent distribution volume was significantly reduced(P<0.05).CONCLUSIONS Luteolin solid dispersion can improve in vitro dissolution and bioavailability of luteolin in Beagle dogs.
作者
黄子婷
王梦颜
常金花
刘沛
王汝兴
刘喜纲
HUANG Ziting;WANG Mengyan;CHANG Jinhua;LIU Pei;WANG Ruxing;LIU Xigang(Institute of Chinese Materia Medica,Chengde Medical University,Hebei Chengde 067000,China)
出处
《中国药房》
CAS
北大核心
2024年第10期1215-1219,共5页
China Pharmacy
基金
河北省高等学校科学研究项目(No.ZD2022-121)
承德医学院自然科学研究计划项目(No.202010)。
