Pharmacokinetics and bioequivalence of evodiamine butyryl derivative-loaded lipid nanoparticles in rats / 中草药

Objective To study the pharmacokinetic characteristics and bioequivalence of evodiamine butyryl derivative (EAB) and evodiamine butyryl derivative-loaded lipid nanoparticles (EABLN) in rats. Methods EABLN were prepared by a film ultrasound method, 16 male SD rats were randomly divided into two groups, and their blood were extracted from eye socket after they were intragastric administrated EAB or EABLN (100 mg/kg) for a given time period. Plasma concentration of EAB was determined by HPLC, then pharmacokinetic data, bioequivalence between EAB and EABLN were analyzed by DAS software. Results The main pharmacokinetic parameters of EABLN were listed, AUC(0-72 h), Cmax, and tmax were (11 535.39 ± 261.08) μg∙h/L, (886.73 ± 15.40) μg/L, and (2.00 ± 0.17) h, respectively. Relative bioavailability of EABLN to EAB was 143%, the bioequivalence of AUC(0-72 h) and Cmax in EAB and EABLN were eligible, but bioequivalence of tmax was not eligible. Conclusion EABLN improved the pharmacokinetics of EAB in rats, meanwhile, oral bioavailability of EAB was significantly increased, and there was not bioequivalence between EABLN and EAB.

In vitro release and in situ gastrointestinal absorption of evodiamine butyryl derivative-loaded solid lipid nanoparticles / 中国药理学通报

Aim To prepare evodiamine butyryl deriva-tive (EBD) and evodiamine butyryl derivative-loaded solid lipid nanoparticles (EBDLN), and study its re-lease in vitro,and to investigate its in situ gastrointesti-nal absorption. Methods EBD was prepared by a one-step synthetized method, and then EBDLN was prepared by a film dispersion method. Dynamic dialy-sis was used to evaluate drug release in vitro,and sin-gle-pass gastrointestinal perfusion was employed to study the gastrointestinal absorption of EDM,EBD and EBDLN. Results In identical release media, there were identical drug release tendencies of EBD and EB-DLN, but the release rate of EBDLN was faster than EBD. Compared with EDM and EBD, the Kavalues and Pappvalues of EBDLN in every perfusion segment increased significantly. The Kaof EBDLN in stomach, duodenum, jejunum, ileum and colon was 110.14-fold,56.70-fold,51.23-fold,45.70-fold and 127.23-fold of free EDM respectively. The Pappvalue of EB-DLN was 9.74-fold, 4.48-fold, 3.82-fold and 11.3-fold of that of free EDM. Conclusion EBDLN has sustained effect and can enhance the gastrointestinal absorption of EDM and EBD.