摘要
目的研究阿魏酸在自制线性微透析探针上的体内外回收率与灌流速度、药物浓度之间的关系,并对自制阿魏酸乳剂在大鼠上进行经皮皮肤药动学研究。方法采用HPLC测定透析液中阿魏酸浓度,考察不同灌流速度、不同药物浓度对探针体外正、反向回收率和体内反向回收率的影响,采用微透析技术进行经皮皮肤药动学研究。结果自制探针性质稳定;在所研究的浓度和灌流速度的范围内,探针回收率与阿魏酸的药物浓度无关,与灌流速度成反比;探针体外正、反向回收率在灌流流速1.0、2.0μL·min^(-1)时有显著性差异(P<0.05),探针体外正、反向回收率在3.0μL·min^(-1)无显著性差异(P>0.05);体内反向回收率低于体外反向回收率,与体外正向回收率无显著性差异(P>0.05)。大鼠经皮药动学表明,阿魏酸乳剂(8.75 mg·cm^(-2))可在体内维持长时间的药物浓度,AUC0-10 h为(128.30±23.51)mg·h·L^(-1),ρmax为(19.08±4.39)mg·L^(-1)。结论在阿魏酸的经皮皮肤药动学研究中,可采用体内反向回收率作为药物的探针回收率来校正;阿魏酸乳剂的经皮吸收能力较好,能长时间释放药物,有望成为新的给药剂型。
OBJECTIVE To investigate the relationship between the recovery of ferulic acid on self-made linear microdialysis probes and the perfusion speed and drug concentrations and study,transdermal pharmacokinetics of self-made ferulic acid emulsion in rats.METHODS The ferulic acid in microdialysate was determined by HPLC.The in vitro recovery of ferulic acid was studied using positive dialysis and retrodialysis methods at different flow rates and concentrations.And the in vivo recovery of ferulic acid was studied using retrodialysis methods.The transdermal pharmacokinetics in skin was evaluated using microdialysis.RESULTS The self-made probe was stable.Over the perfusion flow rates and drug concentrations range studied,the probe recovery of ferulic acid was independent of drug concentrations,inversely proportional to the perfusion flow rates.The positive dialysis and retrodialysis recovery of the probe in vitro was significantly different at the perfusion flow rate of 1.0 or 2.0μL·min^(-1)(P<0.05),and there was no significant difference at 3.0μL·min^(-1)(P>0.05).The retrodialysis probe recovery in vivo was lower than that obtained in vitro,and was no significant difference from the positive dialysis probe recovery in vitro.The transdermal pharmacokinetic results of self-made ferulic acid emulsion showed that it could maintain the drug concentrations for a long time.The AUC0-10 h andρmax of transdermal administration(8.75 mg·cm^(-2))was(128.30±23.51)mg·h·L^(-1)and(19.08±4.39)mg·L^(-1),respectively.CONCLUSION The retrodialysis probe recovery in vivo method is suitable for ferulic acid skin pharmacokinetic study.The ferulic acid emulsion has good skin absorption and long-time substained release,which can be developed as a novel transdermal preparation.
作者
晏娜
徐宇琦
汤湛
李秀敏
王俏
YAN Na;XU Yu-qi;TANG Zhan;LI Xiu-min;WANG Qiao(Department of Phamacy,Jin Hua Municipal Maternal and Child Health Care Hospital,Jinhua 321000,China;Institute of Materia Medica,Hangzhou Medical College,Hangzhou 310013,China)
出处
《中国药学杂志》
CAS
CSCD
北大核心
2021年第2期115-121,共7页
Chinese Pharmaceutical Journal
基金
浙江省神经精神疾病药物研究重点实验室资助(2019E10021)。
关键词
阿魏酸
微透析
探针回收率
体内
体外
经皮药动学
ferulic acid
microdialysis
probe recovery
in vivo
in vitro
transdermal pharmacokinetics
